[1] Founded in 1999 in the wake of passage of California Proposition 209,[3] Preuss uses an intensive college preparatory curriculum to educate low-income students between sixth and twelfth grade,[4] hoping to improve their historical under-representation on the campuses of the University of California.

[10][11] Between 2007 and 2012 Preuss has consistently been listed among the top 50 American high schools by both Newsweek and U.S. News & World Report.

It was their belief, as expressed by Cecil Lytle, provost of Thurgood Marshall College, that public universities were not active enough in creating educational opportunities for the state's most disadvantaged youth.

[13] Faculty members Hugh Mehan and Peter Gourevitch proposed establishing a college-preparatory school that would admit only low-income youths with the potential of becoming first-generation college students.

[3] In the new proposal, the project was to be mostly privately funded and was to have an oversight agency known as the Center for Research on Educational Equity, Access, and Teaching Excellence (CREATE).

[14] This second proposal was brought to the regents and, assisted by public outcry against the university and positive press for the school from The San Diego Union-Tribune, The Sacramento Bee, and the Los Angeles Times, it was approved.

[4] Alvarez in turn selected Janis Gabay, 1990 National Teacher of the Year, to head the faculty.

The group included about 50 students in each of three grades—sixth, seventh, and eighth—and the school continued to add a new sixth-grade class each fall until the intended total enrollment of 800 was reached.

Gompers Middle School, also founded by Cecil Lytle, was modeled after Preuss and took advice from CREATE.

[16] When Gompers first opened, much of its curriculum, faculty development, and community outreach plans were based on those in place at Preuss.

[17] Southeastern San Diego–based Lincoln High also used Preuss as a guide, and the University of California, Davis, (UC Davis) and the University of California, Berkeley, (UC Berkeley) studied it while designing their own high schools for disadvantaged youth.

"[19] Despite this goal, finding available space on UCSD's campus for a full high school facility proved challenging.

For the first year of its existence, Preuss was housed on the campus of the Thurgood Marshall College, in a temporary bungalow facility known as "La Casa", surrounded by eucalyptus trees and within walking distance of UCSD's main library, Geisel Library.

[20] The campus cost about $14 million, all of which was procured from community donors and organizations during a five-month fundraising campaign.

During the 2007 school year, a secondary physical education field was paved over and converted to two additional bungalow buildings intended to be used for music and the arts.

Preuss staff are also responsible for distributing application materials to local churches and libraries and community organizations like the San Diego Urban League and the Parent Institute.

[7] This is divergent from SDUSD's demographics, which is 46% Hispanic, 15% Asian and Pacific Islander, 12% African American, and 24% White.

[23] Throughout this curriculum, Preuss students are required to take courses at the advanced placement (AP) level, when offered.

This homeroom-like experience enables one teacher to become well-acquainted with students, their growth, their families, and their domestic situation.

Each trimester, UCSD provides nearly 100 classroom tutors to Preuss through a university course on educational equity.

[34] These results led San Diego Magazine to name Preuss one of the city's great schools.

[10] In September 2010, U.S. Secretary of Education Arne Duncan announced that Preuss had been selected as one of the nation's Blue Ribbon Schools for 2010.

All Preuss teams compete in Division IV of the San Diego Section of the California Interscholastic Federation.

A majority of Preuss clubs and organizations meet after school until 5:20 p.m., when the late-activity buses take up to 256 students home.

Following this many students have attempted to form other sport-related clubs (for example, boys' volleyball) to widen the sports club/activity selection range, but have been denied due to lack of facilities.

For four years running, the Preuss School has collaborated with the Sanford Burnham Prebys Medical Discovery Institute on an internship program.