Our Lady of the Lake University was the first San Antonio institution of higher education to receive regional accreditation.

As part of its mission to provide education to those with limited access, the university introduced the Weekend College concept at the San Antonio campus in 1978.

OLLU began offering "weekend degree" programs at Lone Star College - North Harris in 1986.

The Houston program would move to the Lone Star College University Center in 2012, and construction would be completed on its stand-alone campus, located off Beltway 8 near Interstate 45, in 2018.

[7] In 2008, the university began a partnership with school districts in the Rio Grande Valley that would eventually evolve into its satellite campus in La Feria, Texas.

Her resignation followed what the San Antonio Express-News characterized as "months of tumult in which students and faculty protested Pollack's decision to eliminate a dozen degree majors, including religious studies and Mexican-American studies, which some considered at the core of the Catholic school's mission and identity.

"[9] Sister Jane Ann Slater, CDP served as interim president until Diane Melby was appointed to the post in July 2015.

[12] Firefighters suspect that the fire started on the fourth floor of the Main building due to an electrical short.

Our Lady of the Lake University also offers classes on its satellite campuses in The Woodlands, near Houston, and in the Rio Grande Valley in La Feria, Texas.

[15][16] On December 12, 2020, the Saints men's basketball team defeated NCAA Division I member Texas State 61–58.

They also made their ninth appearance in the NAIA National Tournament, losing to Wayland Baptist in the opening round.

[21] On February 12, 2022, university play-by-play announcer Michael Thompson fell down the bleachers at a women's basketball game after suffering a cardiac arrest.

[25] On April 29, 2023, the Saints men's track and field team won their first conference championship in school history.

[34] OLLU previously hosted weekend classes at Brookhaven College in Farmers Branch, Texas, near Dallas.