[10] Saint Leo was one of the first American universities to provide distance learning opportunities to students, beginning with educating military men and women in 1973 during the Vietnam era at the height of the anti-war movement.

[15] Saint Leo traces its history to August 10, 1881, when Edmund F. Dunne, a former chief justice of the Arizona Territory, gained control of 100,000 acres in Florida.

[18] In 1888, Saint Vincent Archabbey transferred control of the colony to Mary Help of Christians Abbey (commonly called Maryhelp) in Belmont, North Carolina.

[19] In February 1889, Leo Haid, Abbot of Maryhelp Abbey, accepted a gift from Edmund Dunne of 36 acres on Lake Jovita for the founding of a Benedictine College.

[27] Today, he and the welcoming Benedictines are honored with a sculpture titled A Spirit of Belonging,[28] which was dedicated at University Campus in 2013.

[30] The Saint Leo College Prep School athletic teams were known as the Lions, and their colors were purple and gold.

[41][42] St. Leo University has since closed many of its satellite locations, eliminated 111 faculty/staff positions, cut three degree programs, and phased out six NCAA division II teams, facing continuing enrollment declines and financial issues.

[40] Since 1959, when the junior college was started, Saint Leo has had 11 presidents:[43] In 2024, Saint Leo University accepted 80.1% of undergraduate applicants, with admission standards considered moderate, applicant competition considered very low, and with those enrolled having an average 3.1 high school GPA.

[45] In the 2021 U.S. News & World Report Best Colleges rankings, Saint Leo was named #26 overall in the Regional Universities South category.

Saint Leo University's SGU has implemented many projects and initiatives across campus that help students succeed with memories; most notably, being the Lion Statue at the school's entrance (2018), Food Pantry (2018;2022),Scholarship Program (2018), and the Greek Street Benches (2024).

Some of SGU's current and former signature events included Halloween Horror Nights at Universal Studios, campus laser tag, Moonlight Breakfast, and a "Spring Fling" weekend featuring artists such as Lonestar, Everclear and Nick Hagelin from The Voice.

They participate as a member of the National Collegiate Athletic Association's Division II in the Sunshine State Conference (SSC).

Men's sports include baseball, basketball, cross country, golf, lacrosse, soccer, and tennis; women's sports include basketball, cross country, golf, lacrosse, soccer, softball, tennis, acrobatics and tumbling, volleyball and beach volleyball.

The university discontinued men and women's swim, track, and cross country programs in Spring of 2023 “to help ensure the strength and long-term vitality of the university's Athletics program and is a part of Saint Leo University's larger efforts to streamline and focus its program offerings.”[57] The school won its first NCAA Division II National Title in 2016[58] when the Lions' men's golf team defeated Chico State, 3–2, in the NCAA DII Championship round at Green Valley Ranch Golf Club in Denver, Colorado as part of the 2016 NCAA Division II Spring Championships Festival.

Saint Leo also played host to the 2016 NCAA Division II Cross Country Championships at The Abbey Course.

Saint Leo University has produced thousands of alumni over the years, including Charles Henri Baker, a Haitian industrialist and presidential candidate; politicians Richard Corcoran and Ed Narain; Cerelyn J. Davis, Memphis Police Department Chief; George N. Turner, former Atlanta chief of police; musicians Stephen Stills and Desi Arnaz; Major League Baseball executive J. P. Ricciardi; Academy Award-winning actor Lee Marvin; and Major League Baseball player Bob Tewksbury.

In January 2014 Saint Leo University received a construction permit for a Low Power FM Station to operate on 92.7 MHz.

WLSL-LP covers the communities of Saint Leo, Dade City, and San Antonio and can be heard in a car radio as far north as Ridge Manor and south of Zephyrhills.