On January 15, 1850, the Indiana General Assembly adopted Ovid Butler's proposed charter for a new Christian university in Indianapolis.

The university's charter called for "a non-sectarian institution free from the taint of slavery, offering instruction in every branch of liberal and professional education".

The Bona Thompson Library at the intersection of Downey and University avenues, designed by architects Henry H. Dupont and Jesse T. Johnson, is the only remaining building, although several buildings that housed faculty remain, including the Benton House.

Renamed as Butler College, the school constituted the undergraduate and liberal arts organ of the new university.

[5] Enrollment at Butler increased following the end of World War I, prompting the administration to examine the need for a larger campus.

[2] In 1928, the first building completed on the Fairview campus was Arthur Jordan Memorial Hall, designed by Robert Frost Daggett and Thomas Hibben.

[4][5] Following World War II, construction began on the student center, Atherton Union (designed by McGuire and Shook).

Clowes Hall, which opened in 1963, was co-designed by Indianapolis architect Evans Woollen III and John M. Johansen (of New Canaan, Connecticut).

Ten years following the construction of Clowes Hall and Irwin Library, the science complex of Gallahue Hall and the Holcomb Research Institute (now Holcomb Building) were built, completing the U-shaped complex of academic buildings.

[4][5][14] In 1990, the Residential College, designed by James and Associates, was completed, becoming the university's last major construction project of the 20th century.

The university emphasizes the practicality of knowledge and offers individual attention to its students with its small class size and no teaching assistants.

[24] Greek life is a popular option at Butler with over 35 percent of undergraduates becoming members of social fraternities or sororities.

The women's golf team at Butler joined the Metro Atlantic Athletic Conference, as the A-10 sponsors the sport only for men.

Butler won the James J. McCafferty trophy, awarded annually by the Horizon League for all-sports excellence based on conference championship points, seven times, including three-straight from 1996–97 to 1998–99 and back-to-back years in 2001–02 and 2002–03, 2006–07, and 2009–10.

[34] With a total enrollment of only 4,500 students, Butler is the smallest school to play for a national championship since the tournament expanded to 64 teams in 1985.

After Valparaiso head coach Stacey Adams agreed to play for the helmet, Butler equipment manager John Harding put the trophy together.