Angelo State University was created as Angelo State College in 1965 by an act of the 58th Session of the Texas Legislature in 1963. The history of the University, however, can be traced to 1928 when San Angelo College was established, following a municipal election held in 1926. Located in San Angelo, Texas, and organized as part of the city school system, the two-year college for many years occupied a site on North Oakes Street near the commercial center of the city. The voters of Tom Green County in 1945 created a County Junior College District and elected the first Board of Trustees. In 1947, the first building was constructed on the present University site.

Angelo State University has experienced a rapid transition from the status of a regional junior college to that of an accredited senior institution of higher learning. The transfer of authority from the Board of Trustees of the junior college to the Board of Regents, State Senior Colleges, became effective on September 1, 1965. In May 1967, the first baccalaureate degrees were awarded. The name of the institution was changed to Angelo State University in May 1969.

Angelo State University was designated as a member of the Texas State University System in 1975, along with Sam Houston State University, Southwest Texas State University, and Sul Ross State University, when the 64th Texas Legislature changed the name of the governing board to Board of Regents, Texas State University System. In September 1967, Dr. Lloyd Drexell Vincent became the second President of Angelo State College, succeeding Dr. Raymond M. Cavness who first held that post. Dr. Vincent served as President until his death on August 5, 1994.

Following the death of President Vincent, Michael P. Ryan was named Interim President by the Board of Regents, Texas State University System, on August 9, 1994. On January 25, 1995, Dr. E. James Hindman became the third President of Angelo State University.

The 268 acre (1.1 km²) campus has changed significantly since 1965 as a result of the development of an ultramodern physical plant now valued at over $150 million. The Porter Henderson Library was completed in the fall of 1967, and in the spring of 1968 the Raymond M. Cavness Science Building was opened. An academic building and a ten-story women's high rise residence hall and accompanying food service center were opened in September 1968. A second ten-story residence hall for men opened in September 1969. The modernization and expansion of the Houston Harte University Center was completed during the summer of 1971, and a physical education complex was opened in the summer of 1972.

The Robert and Nona Carr Education-Fine Arts Building, completed during the spring of 1976, provides ultramodern facilities for the Departments of Education, Art and Music, and Communications, Drama, and Journalism. In addition to an extensive array of teaching facilities, many special use areas are incorporated in the building, including the theatre, recital hall, band hall, and an area for art design and ceramics. Construction was completed during the summer of 1975 on a facility at the University's Management, Instruction, and Research Center operated at the O.C. Fisher Lake on 4,643 acres (19 km²) of property which Angelo State has under long-term lease from the U.S. Corps of Engineers, Department of the Army. These facilities support the programs in animal science and biology and a wide range of management and research activities. A multipurpose sports complex for men and women was completed in 1979 which includes an all-weather Tartan track, two regulation softball fields, tennis courts, improved practice fields for football, and ultramodern facilities for dressing and training. The 60,000 square foot (5,600 m²) Emil C. Rassman Building, completed during the summer of 1983, houses the Department of Business Administration, the Department of Accounting, Economics, and Finance, and Department of Aerospace Studies, as well as the office of the Dean of the College of Professional Studies.

The $8 million Lloyd D. and Johnell S. Vincent Nursing-Physical Science Building was completed during the 1985 Spring Semester. Located across the mall from the Physical Education Building and the Emil C. Rassman Building, the building contains approximately 73,000 square feet (6,800 m²) arranged over two floors. The building houses the University's nursing program, the Physics Department, and offices for the Dean of the College of Sciences and the Dean of the Graduate School. Specialized teaching and laboratory facilities are included for physics, physical science, geology, nursing, and mathematics. A highlight of the building is a planetarium featuring a 50 foot (15 m) dome and seating for 114. The facility is used as a lecture hall and for other special programs. It is also used in conjunction with academic courses in astronomy and for public shows.

The 86,000 square foot (8,000 m²) Mathematics-Computer Science Building, completed in 1996, houses the Department of Mathematics and the Department of Computer Science as well as facilities to support the University's mainframe computing services. Other recent additions include expansion of the Cavness Science Building, construction of the new Texan Hall residences, and adding an additional floor to the Porter Henderson Library to accomodate the Communications, Drama, & Journalism department and Honors Program.

The Graduate School at Angelo State University was authorized by the Board of Regents, State Senior Colleges, on May 15, 1970, and approved by The Texas Higher Education Coordinating Board, on October 19, 1970. The first graduate students were enrolled in the Fall Semester 1971. Over 6,606 students have been admitted to the graduate program since it was initiated. The baccalaureate degrees of these graduate students were awarded by 617 different colleges and universities from every region of the nation and several foreign countries.

In addition to the rapid progress in the development of the physical plant and the expansion of the academic programs at Angelo State, significant strides have been taken in the development of a first-rank faculty. Approximately 61 percent of the faculty in the undergraduate baccalaureate degree programs now hold the doctoral degree granted by 55 different universities, representing all regions of the nation.