The late 1960s and early 1970s were a period of direct action in Native American politics. The occupation of Alcatraz Island in 1969 had electrified Indigenous communities nationwide, and the tactic of claiming surplus federal land spread. The Army's radio transmitter site near Davis, formally known at various times as the Sacramento Valley Radio Transmitting Station and the U.S. Army Strategic Communications Command facility, was mostly deactivated and operating in caretaker status. Native American activists occupied the grounds, and the Army, with no active mission to protect and no classified materials on site, chose not to force them out. A group of Native American academics at UC Davis, including David Risling, Jack D. Forbes, Carl Gorman, Kenneth Martin, and Sarah Hutchison, formed a board of trustees and applied for use of the site. UC Davis had also applied, proposing a primate research lab. The organizers protested, UC Davis withdrew, and in 1971 the federal government conditionally granted the land to what would become D-Q University.

What made D-Q unique among tribal colleges was its independence. The other five institutions founded between 1968 and 1972 were each affiliated with a single federally recognized tribe and located on reservations. D-Q had no tribal sponsor and no reservation. Its organizers were drawn from Native American activists across California, many of them members of different federally recognized tribes, united by the conviction that mainstream universities were failing Indigenous students. The college was founded to serve both Native American and Chicano students, with a mission to preserve traditional values, protect Native American religious practices, establish a research institute, and develop field-based education for students who could not attend classes on campus. Together, the six founding tribal colleges created the American Indian Higher Education Consortium in 1972, a network that today encompasses 34 recognized tribal institutions enrolling more than 30,000 students.

D-Q obtained accreditation in 1977, six years after opening, but stability always proved elusive. The college competed for students and funding with mainstream universities that were simultaneously launching their own Native American studies programs. Faculty recruitment was difficult. Funding was precarious. The board of trustees turned over frequently, and the institution's independence, the very quality that made it distinctive, also left it without the steady support that reservation-based tribal colleges received from their sponsoring nations. By the early 2000s, enrollment had declined sharply. In 2003 and 2004, the Bureau of Indian Affairs cut funding due to insufficient Native American enrollment, and the Department of Education followed. The college lost its accreditation in 2005 and stopped offering regular classes. In 2008, students and supporters who refused to abandon the campus were arrested during several occupations of the grounds.

Even after losing accreditation, the campus did not go silent. Annual powwows continued through 2013, drawing tribal representatives from across California and beyond. Veterans Day powwows persisted through at least 2017. Students and instructors who remained on the grounds used the facilities for classes, gatherings, and ceremonies. The buildings still bore traces of their military past: chairs and tables stamped with Army property markings, graffiti from the early 1970s occupation visible on interior walls. By 2015, the board of trustees had expanded from four to fourteen members representing numerous California tribes, and a curriculum committee was assessing the educational needs of Native Americans in the state. The board signed a memorandum of agreement with the Inter-Tribal Council of California in 2012, working toward reopening. A satellite campus persists as Kumeyaay Community College. The dream of D-Q has not died, though it has changed shape considerably since the days when activists walked onto a decommissioned antenna farm and imagined a university.