Founded in 1885 by John Ireland, archbishop of Saint Paul and Minneapolis, St. Thomas began as an all-male, Catholic seminary.

Initially, the school gave out two-year diplomas in commercial and classical programs before awarding its first academic degrees in 1915.

From the late 1920s through the mid-1930s, the Holy Cross Fathers, who run the University of Notre Dame, controlled the college's administration.

After the war, in 1948, the college established "Tom Town" on the eastern end of the lower quadrant, which is currently the site to the O'Shaughnessey-Frey Library and O'Shaughnessey Education Center.

Tom Town, made of 20 double-dwelling huts, consisted of white, barracks-like housing units for faculty, students, and their families.

The main campus, built on a farm site once considered "far removed from town", is located where St. Paul's Summit Avenue meets the Mississippi River.

The site was farmed by ex-Fort Snelling soldier William Finn, who received the property as a pension settlement after he accidentally shot himself in the hand while on guard duty.

[citation needed] In early 2012, St. Thomas completed the final stage of its three-building expansion on the St. Paul campus.

[12] The Anderson Athletic and Recreation Center has a field house, basketball arena, weight room, and swimming pool.

[citation needed] The new Anderson Student Center is home to new food venues, as well as entertainment options, including a game room and bowling alley, and a coffee shop.

[15] It is connected to the Iverson Center for Faith and Ireland Hall via tunnel and sits on the site of the former John Paul II dormitory.

[16][17] In 2021, St. Thomas moved forward with plans for a new $110 million, 130,000 square foot building on South Campus called Schoenecker Center.

Artist Mark Balma created one of the largest frescoes in the United States on the arched ceiling of its atrium.

[21] The seven-panel, 1,904 square feet (176.9 m2) fresco was completed in the summer of 1994 and portrays the seven virtues discussed in the writings of St. Thomas Aquinas.

The deal included the entire 180-acre property and all the buildings except for the Winton Guest House, which was designed by architect Frank Gehry.

[27] St. Thomas also houses the Saint Paul Seminary School of Divinity, which offers master's- and doctoral-level degrees oriented to theological study and the practice of ministry.

In 2012, St. Thomas played for the first time in the Stagg Bowl in Salem, Virginia, which is the Division III Football National Championship game, against the University of Mount Union, losing 28-10.

Residence halls on campus are named after Archbishops of St. Paul-Minneapolis, such as William O. Brady, Austin Dowling, and John Ireland.

Recently the department of residence life has purchased additional buildings on what they are calling 'mid-campus' in the area between Grand and Summit Avenues.

These include Sustainability, Aquinas Scholars, Tommies Do Well(ness), Pathways to Engineering, eMedia, Bridging Divides, Catholic Studies, Major Explorers, and Business for the Common Good.

[41] In 2007, the president of the University of St. Thomas, Father Dennis Dease, cancelled a planned speech by Nobel Peace Prize laureate and anti-apartheid figure, Desmond Tutu, on the grounds that his presence might offend some members of the local Jewish community.

[42] Members of the anti-Zionist group Jewish Voice for Peace led an email campaign calling on St. Thomas to reconsider its decision,[43] which the president did and invited Tutu to campus.

[44] Tutu declined the re-invitation, speaking instead at the Minneapolis Convention Center at an event hosted by Metropolitan State University.

In 2008, plans were announced to the public that the theater department at the University of St. Thomas was to be dissolved and that the school would no longer offer this major.