He originally intended to construct a full college campus on his 280-acre (1.1 km2) property in nearby Ann Arbor, known as Domino's Farms.

[8] After being denied zoning approval by Ann Arbor Township to build a larger campus near Domino's Farms, Monaghan decided to move the college to Florida.

[9][10] In August 2003, the university opened an interim campus in The Vineyards in Naples, Florida, enrolling some 100 undergraduate students, 75 of whom were freshmen.

The Barron Collier family donated the land in southwest Florida for the campus, joining Monaghan in the enterprise as 50% partner.

He was dismissed from that position in 2009, stating he was fired the second time because of a conversation he had with Academic Vice President Jack Sites about administrative policies harming the university's finances.

[18] Monaghan planned to continue to expand the university and hoped to one day have an enrollment over 5,000, Division I athletics and an academic reputation as "a Catholic Ivy", however as of 2024, only has about 20 percent of this goal.

Monaghan said in 2012 that Ave Maria's construction cost estimates doubled over three years, requiring the university to cut back on planned buildings.

[23] According to Towey, for a period of time the university survived through Monaghan's funding of a ten million dollar annual deficit.

Towey credits his efforts at controlling financing costs, along with increased contributions, with placing the university back on a firm financial footing by 2014.

[34] Howard Simon, executive director of the American Civil Liberties Union branch in Florida, challenged the legality of the restriction of sales of contraceptives.

"[36] An opinion column in The Wall Street Journal quoted an Ave Maria faculty member who called it a "Catholic Jonestown".

[37] In response, Monaghan announced a milder form of civic planning in which the town could mostly grow on its own, except that it would not have sex shops or strip clubs, and store owners would be asked rather than ordered not to sell contraceptives or porn.

[46] On October 7, 2011, the local ordinary, Bishop Frank Joseph Dewane, formally recognized the institution as a Catholic university pursuant to the code of canon law.

The pope’s apostolic constitution, Ex Corde Ecclesiae (From the Heart of the Church), set the foundations for the academic and spiritual standards for Ave Maria University.

[49] Ave Maria University offered study abroad programs in Gaming, Austria, and in San Marcos, Nicaragua.

[51] The new campus is located in the town of Ave Maria, Florida, 17 miles (27 km) east of Naples in rural Collier County.

[52] The Ave Maria Oratory, a large Gothic-inspired structure located at the center of town, was constructed by the university and currently serves as the parish church.

[58] Ave Maria University is home to a museum about the life and legacy of Mother Teresa, honored in 1979 with the Nobel Peace Prize.

Artifacts include a piece of her sari, her crucifix and rosary, and letters from her and former Ave Maria University president, James Towey.

The Missionaries of Charity also provided storyboards – in Spanish and English – that include rare photographs of Mother Teresa and tell the story of her life.

Originally owned by the university and called the Oratory, the building was purchased in January 2017 by the Diocese of Venice, and its status was raised to parish church.

Ave Maria competes in 24 intercollegiate varsity sports: Men's sports include baseball, basketball, cross country, football, golf, soccer, swimming, tennis, track & field (indoor and outdoor) and ultimate frisbee; basketball, beach volleyball, cross country, dance, golf, lacrosse, soccer, softball, swimming, tennis, track & field (indoor and outdoor) and volleyball.

[76] In 2023 Ave Maria University launched a series of free online video courses titled, "The Pursuit of Wisdom."