Regis Jesuit High School traces its origins to the College of the Sacred Heart and was founded in 1877 in Las Vegas, New Mexico by Jesuits from Naples, Italy. In 1884, the Jesuits opened a second school in Morrison, Colorado. Four years later, the Las Vegas and Morrison schools were merged into College of the Sacred Heart and moved to West 52nd and Lowell Blvd. in Denver. Later the schools were named for St. John Francis Regis, a French Jesuit.

In 1921, the high school and college were formally separated into two distinct entities, and in 1979 they became separate corporations. With the completion of a new high school building on the college campus in 1976, Regis Jesuit High School moved out of the Regis University facilities. However, the school soon outgrew that building as well, and it was decided that a new location was needed to allow for future expansion.

On September 16, 1989, the cornerstone was laid for the new campus in Aurora. Classes began at this location in September of 1990. In January of 1997, Regis Jesuit purchased 35 additional acres at this site; and on April 11, 2003, the school broke ground for the construction of a new facility for the Boys Division. The Girls Division, with 170 students, opened its doors at St. Catherine's Greek Orthodox Church in August of 2003. In August of 2004, the Boys Division moved into their new facility; and the Girls Division moved into the newly-renovated original facility. These moves brought the two Divisions together on the Campbell Campus, named for the benefactor who donated the original parcel of land in Aurora, allowing the school to continue its rich traditions.

Further connection between the Divisions was forged when the Performing Arts Center & Student Commons building was added to the campus. Opened in February 2013, the building houses the school's performing arts classrooms for music and theatre, including a 485-seat theatre called The Z, as well as the Schmidt Family College Counseling Center and student media lab. The common spaces, including a snack bar, draw boys and girls together before and after school and during lunch to socialize and strength ties through their shared experience as Regis Jesuit Raiders. In June 2015, the new building was christened the Steele Center, in honor of Rev. Philip G. Steele, SJ '66, who served as the school's President from 2006-15.