Victor C. Kays of Illinois was recruited as the first principal (later changed to president), and he immediately began recruiting faculty and building the new campus on the donated land. While work on the buildings continued, the first classes opened on Oct. 3, 1910 in downtown Jonesboro in the old Elks Lodge Hall above a jewelry store on Washington and Main. The 189 enrolled students were taught by a faculty of eight, including Kays. Staff consisted of a secretary, a superintendent of farms and a superintendent of residence halls. Work not done by faculty or staff was performed by students, who paid no tuition but were expected to work on the campus.

Despite its agricultural focus, the "Aggie School" offered a well-rounded curriculum from the beginning, and many of the general education courses were taught using college level textbooks. Kays also introduced athletics during the first year, as well as fine arts programs and a range of extracurricular activities.

By the 1920s, academic work on campus had evolved into a junior college curriculum. The change came about during World War I, when the Board of Trustees sought to host a Student Army Training Corps (SATC) unit on campus. After Kays learned that such units could only be housed at institutions with at least junior college status, he immediately broadened the curriculum to qualify. The new status was formally recognized in 1925 when the legislature changed the school's name to First District Agricultural and Mechanical College.

Though the SATC was short-lived on campus, due to the fact that the war ended just two months after the unit was assigned, it was replaced in 1923 by a larger military presence when an Arkansas National Guard Unit--Battery C, 206th Coast Artillery, Anti-Aircraft-was assigned to the school. A new Armory was built to accommodate the unit and included a gymnasium that was the largest in the state.

Along with its two-year college curriculum, Aggie also opened a Training School in the 1920s that included kindergarten through grade 12. The school was used as a practice laboratory for students who wished to become teachers, and it operated until the 1950s when education majors began doing their "practice teaching" in area schools. The Training School is memorialized today through an Arch that once marked the entrance to the college and is now the oldest structure on campus. It was donated by the Training School Class of 1927.

The 1930s decade had auspicious beginnings when a major fire consumed the Administration/Classroom Building in the early morning hours of Jan. 12, 1931, the first day of spring semester classes. In spite of the total loss, President Kays found temporary class locations around campus, including the Dairy Barn, and classes continued on schedule.

Construction also began immediately on a new Administration/Classroom Building, which opened in 1932. It was named Wilson Hall, after Trustee R. E. Lee Wilson of Mississippi County, who provided most of the men, equipment, and mules for the construction of the new building. The building is a visible reminder of the long association with the Wilson family, including the establishment of the Wilson Award in 1933, which recognized the outstanding male and female graduates each year. Since the 1980s, there has been one Wilson Award each year to the outstanding graduate, rather to the outstanding male and female.

By the 1930s, the academic program had evolved into a full four-year college curriculum, and the first four-year degrees were awarded in 1932. The following year, Aggie's name was changed to Arkansas State College.

Despite the Great Depression, campus enrollment and facilities grew during the 1930s. Much of the growth was due to the ingenuity of President Kays who, working closely with U. S. Sen. Hattie Caraway of Jonesboro, devised a number of strategies for attracting federal monies to the campus. Thanks to work-relief programs and Reconstruction Finance Corporation funds, residence halls were built to accommodate the increasing number of students and a new science building was completed, along with Wilson Hall and other facilities. In recognition of her assistance, Senator Caraway received the school's first honorary doctorate.

ROTC was established as an Artillery unit on Jan. 20, 1936, with the basic course being mandatory instruction for all male students.

The growth experienced during the school's early years and throughout the 1930s was dramatically reversed in the early 1940s, beginning with the activation of the campus National Guard unit in January 1941. When war was declared in December 1941, enrollment dropped significantly as men went off to war, and eventually student numbers fell to a low of 114 students-mostly females.

Once again, President Kays turned to Washington, D. C. and to Sen. Hattie Caraway. Kays managed to keep the doors open and reverse the enrollment numbers by becoming the training school for a number of military units. These included the Army Administration School, the Army Air Cadets, and an Army Specialized Training Program in engineering. In addition, the campus provided work for the German prisoners of war housed at the nearby Civilian Conservation Corps (CCC) camp.

When the war was over, the campus experienced the opposite problem. With the influx of World War II veterans, the campus was bursting at the seams, and temporary housing had to be provided to accommodate students, including a number with families. The seasoned combat veterans were much different than those who entered campus directly from high school, and they brought their own unique problems and perspectives to campus.

The 1940s also saw administrative change. After 34 years at the helm, President Kays resigned in 1943. He was followed by 1925 Aggie alum, Horace Thompson, who served from 1943-45. Kays returned for an interim period until the arrival of W. J. Edens who served from 1946 to 1951.

Carl R. Reng was recruited from the University of Arkansas to become President of Arkansas State College in 1951, beginning another lengthy presidential tenure. The Reng years were marked by phenomenal growth, as the post-war years led to greater recognition of the importance of a college degree. Reng expanded the size of the campus, adding new acreage as well as new buildings, and aggressively sought faculty and students.

Graduate programs at the master's level were offered beginning in 1955, and that year saw another major change. Walter Strong, Fred Turner, and Larry Williams became the first black students on campus and, although Williams dropped out before graduating, Strong and Turner went on to become the first black graduates. In 1970, Turner returned to the campus as the first black ROTC instructor.

During the 1950s, Arkansas State's growth rapidly outpaced its sister schools also created as part of Act 100 of 1909. The school began comparing itself to the University of Arkansas, rather than its early counterparts, which today have become Arkansas Tech at Russellville, Southern Arkansas University in Magnolia, and the University of Arkansas at Monticello. Thus, as the 50th anniversary of the school approached, Reng began a campaign to achieve university status. Though the effort failed during the 1959 legislative session, it set the agenda for campus activities that led to a successful effort eight years later.

The campus and academic programs continued to grow during the 1960s, as Reng developed the infrastructure and support for university status. After nearly a decade of work, intense lobbying from ASU administrators, and strong support from the Student Government Association and the community, the effort succeeded, and on Jan. 17, 1967, the institution became Arkansas State University.

With the public battle for university status now over, the institution faced other issues in the late sixties and into the early seventies. As at other universities around the country, these years were marked by protests, demonstrations and campus unrest among both students and faculty. At ASU, faculty protested firings and voiced concerns over academic freedom and non-renewal of pre-tenured contracts, while students protested the Vietnam War and mandatory ROTC. In addition, black students had a list of grievances, including a successful campaign to end the playing of Dixie.

Athletics did its part to put the university on the map shortly after the school's new status was achieved. The football team played in the Pecan Bowl for three consecutive seasons-from 1968 through 1970-and won the National Championship in 1970. Baseball came into its own in the late 1960s as well and won three Southland Conference Championships, along with becoming NCAA Mid-West Regional Champions in 1967 and 1968 and placing third in 1968 in the College Division World Series. Basketball fans were treated to performances by All-Americans Jerry Rook and John Dickson, two of the most prolific scorers in ASU basketball history.

ASU's athletic prowess continued into the 1970s, with international recognition coming through the track and field program. In 1972, Hill earned a bronze medal in the 110-meter hurdles in Munich, and the Olympic successes continued into the 1980s, with Al Joyner winning the gold in the triple jump in Los Angeles, and Earl Bell winning the bronze in the pole vault in the same year. Women's athletics also gained new stature at ASU in the 1970s, as women's programs around the country received a boost from Title IX, the federal act requiring equality of opportunity for women.

In 1970 Arkansas State employed Dr. Calvin Smith, who had done his master's work at ASU, to teach in the history department, making him the first black faculty member on campus. Minority enrollment continued to grow, and in 1972, the university had its first all-black Homecoming Court.

Reng retired in 1975 and was followed by several short-term presidents. Ross Pritchard served from 1975 to 1978, followed by Carl Whillock from 1978-1980. Pritchard made great strides in recruiting minority students and faculty, while Whillock introduced a number of programs to recognize academics, including establishment of a Convocation of Scholars Week and an agricultural cooperative program with the University of Arkansas.

When Carl Whillock resigned to enter private business, ASU alumnus and long-time university administrator Eugene W. Smith became interim president prior to the appointment of former Congressman Ray Thornton. During Thornton's tenure from 1980 to 1984, he reinstituted an interdisciplinary Honors Program, established a President's Fellows program, and introduced a strong international element to campus through a contract with the Saudi Arabian government to train Customs officials. His resignation to become president of the University of Arkansas System led to Smith becoming permanent president.

Smith accomplished a number of goals early in his presidency, including opening the ASU Convocation Center in 1987 and leading the university in adapting to new technologies. The celebration of the university's 75th anniversary in 1984 served as the impetus for a number of new programs and traditions on campus, including the Distinguished Alumni program and expanded Faculty recognition programs.

By the time of his retirement in 1992, he had achieved other goals, including the university's first doctoral program in educational leadership, a move to Division 1-A status in athletics, expansion of the library, and inauguration of the university's first capital campaign, which ultimately raised $21 million in gifts and pledges.

When Smith retired in 1992, John Mangieri became president and implemented leadership and quality assurance programs on campus. With his departure in the spring of 1994, Vice President for Academic Affairs Dr. Robert Hoskins served briefly as interim president but died suddenly several months into his term. He was succeeded in the summer of 1994 as interim president by Vice President for Student Affairs Dr. Mossie Richmond. The death of Richmond that fall was the second sudden death of a popular long-time university administrator.

Dr. Eugene Smith served as interim president a second time during the 1994-95 academic year to lead the university in conducting a nationwide search for a president. During that year, he saw the culmination of his earlier library expansion efforts when President William Jefferson Clinton dedicated the completed project and became the first sitting President to visit the campus.

After an extensive search, Dr. Les Wyatt was recruited from the University of Mississippi and arrived in the summer of 1995. Wyatt's presidency ushered in a new era of campus building expansion, continued enrollment growth, new emphasis on research, and new methods of program delivery, including advances in distance learning and development of new campuses and instructional sites throughout the state.

The new millennium brought an enhanced research reputation with the opening of the Arkansas Biosciences Institute, part of a collaborative effort among five institutions to conduct agricultural and medical research to improve the health of Arkansans. Adding to ASU's growing recognition in research, new doctoral programs were added, including PhD's in Environmental Sciences, Molecular Biosciences, and Heritage Studies.

The campus has become increasingly more student-focused, and a number of new facilities have been developed to meet students' needs and interests, including campus housing alternatives and a new Student Union. Campus construction continued in other areas as well, much of it through private gifts, including a $20 million gift from the Reynolds Foundation for a Donald W. Reynolds Center for Health Sciences. In contrast to the many new buildings on campus, one student facility came down with a bang when the Twin Towers residence hall was imploded in front of a huge crowd of spectators in 2008.

Another major change occurred in 2008 when the university's long-time athletic mascot was retired and the ASU Indians became the Red Wolves.

The growth of ASU's sister campuses led to the official creation of a system office in 2006, with Wyatt remaining as president of the System, and Dr. Robert L. Potts becoming the first chancellor for the main campus in Jonesboro. Dr. Potts' term emphasized enrollment growth, continuing expansion of research efforts, diversity initiatives, new facilities to accommodate enrollment growth, and aggressive fund-raising efforts to meet growing campus needs.

Dr. Tim Hudson was appointed chancellor in the spring of 2012. Arkansas State initiated several projects that are transforming the Jonesboro campus into a destination university.  A-State has established the first American-style university campus operated by a U.S. college in Mexico, and joined with New York Institute of Technology to locate a second site of its College of Osteopathic Medicine in a remodeled Wilson Hall.  Preparing the next generation of leaders with a commitment toward a global mindset is an institutional priority. 

Programs to improve residences through living-learning communities, such as the Honors LLC, and the opening of Sorority Row and The Circle have generated an all-time record for Arkansas State’s on-campus student population.  For the past two years, A-State has welcomed the most academically prepared freshman class (i.e., highest ACT scores and high school GPAs).  The Carl R. Reng Student Union has been named one of the top 30 in the country.  Travel through the campus was enhanced in 2017 with the opening of a new street, bordered by a pedestrian and biking trail, connecting Aggie Road with University Loop West on the southwest side of campus.

The fall of 2015 featured the opening of the Humanities and Social Sciences Building, the third largest instructional building on a university campus in Arkansas.

Gov. Asa Hutchinson joined Arkansas State University and New York Institute of Technology leaders June 2, 2016, for the rededication of historic Wilson Hall as home of an additional site of NYIT College of Osteopathic Medicine, which became the state's second medical school.  A $12.6 million renovation and modernization of the 86,000-square-foot building, which opened in 1932 and housed almost every aspect of what was then A & M College, began in September 2015.  NYITCOM at A-State welcomed its first class of 115 medical school students in August.

Dr. Kelly Damphousse became chancellor July 1, 2017, and has kept the university on track for steady growth, enhanced visibility across its major constituencies, and improved retention and the educational atmosphere.

Arkansas Gov. Asa Hutchinson and Queretaro Gov. Francisco Dominguez joined more than 850 dignitaries, guests and students to celebrate the historic grand opening of Arkansas State University Campus Queretaro in September 2017. ASU System President Chuck Welch described the commemoration as the third most important event in the university’s 108-year history. The $100 million, state-of-the-art campus, is the first American-style university in Mexico.  It also incorporates the A-State brand and Red Wolves logo.

Chancellor Damphousse announced the largest individual gift to date in the history of the university, from 1948 alumnus Neil Griffin, in the spring of 2018.  The $10 million gift led to the naming of the Neil Griffin College of Business, along with an endowed chair, endowed professorships, excellence funds, and deanship.  

The largest single gift to the arts at A-State, $6.7 million from the Windgate Foundation, announced in the fall of 2018, is funding construction of the Windgate Center for Three-Dimensional Arts, southeast of the Fine Arts Center.

Construction of the Red Wolf Convention Center and Embassy Suites, south of Centennial Bank Stadium, began in 2018 and the grand opening was held March 5, 2020.  With 203 upscale suites and a 40,000-square-foot convention center, the facility will be the first of its kind in the region.

Expansion of Centennial Bank Stadium with a new press box, suites and club seating, along with expansion and enhancement of the north end zone is complete as a result of surging enthusiasm for the Red Wolves football program, which has won the Sun Belt Conference championship in five of the last eight seasons and made four straight GoDaddy Bowl appearances, followed by the R+L Carriers New Orleans Bowl in 2015, AutoNation Cure Bowl in 2016, and Raycom Media Camellia Bowl in 2017.  In 2018, the team played in the Nova Home Loans Arizona Bowl on Dec. 29, and in 2019 the Red Wolves won the Camellia Bowl.

Since 1928, Arkansas State University has had continuous accreditation by The Higher Learning Commission, which made its most recent comprehensive campus visit in spring 2018.

Construction of the Red Wolf Convention Center and Embassy Suites, south of Centennial Bank Stadium, began in 2018 and the grand opening was held March 5, 2020. With 203 upscale suites and a 40,000-square-foot convention center, the facility will be the first of its kind in the region.

Alumnus and former Army officer Frederick C. Turner, the first African American to serve on faculty at Arkansas State University, is honored in perpetuity following action by the ASU System Board of Trustees on June 3, 2021. The seven-member board voted unanimously to approve a Student Government Association initiative to name the Lieutenant Colonel Frederick C. Turner Jr. Military Science Building. Turner began teaching courses in military science in 1969 as part of the Army Reserve Officers’ Training Corps (ROTC) program.

Windgate Center for Three-Dimensional Arts opened Sept. 13, 2021, with a dedication ceremony and ribbon cutting for the latest facilities expansion for the Department of Art + Design. The $7.9 million facility was made possible through a gift from the Windgate Foundation. The center’s indoor space totals 16,818 square feet, and outdoor working space offers an additional 5,000 square feet. The Windgate Center replaces a New Deal era building that had been repurposed several times.

A-State announced the largest financial contribution in the institution’s history on Dec. 3, 2021, as the Windgate Foundation pledged a $25 million challenge gift toward the construction and maintenance of a new building on campus. The ASU System Board of Trustees voted to accept the gift and designate the facility as the Windgate Hall of Art and Innovation, along with establishing the Art and Innovation District.

System President Dr. Charles L. Welch appointed Dr. Todd Shields, dean of the Fulbright College of Arts and Sciences at the University of Arkansas since 2014, to serve as A-State’s fourth permanently appointed chancellor. A Chancellor Search Advisory Committee representing faculty, staff, students, and community leaders recommended Shields, who began work Aug. 15, 2022.