The original logic for placing a veterinary school at Davis was geographic. In the early twentieth century, of ten veterinary schools in North America, only one stood west of the Rocky Mountains, at Washington State. Four were clustered in the Northeast. This made no practical sense given the enormous livestock and poultry populations of the western states, which needed veterinary care far more than they needed another East Coast program. On May 26, 1944, the Board of Regents voted to establish a veterinary school at Davis and to transfer Berkeley's existing veterinary science research there. It was the first professional school to open on the Davis campus, and it shaped the university's identity in ways that persist today. The school's emphasis on livestock, agriculture, and practical animal medicine reflected the Central Valley around it, a landscape defined by farming on an industrial scale.

William R. Pritchard served as dean from 1962 to 1982, a tenure that transformed the school from a solid regional program into a global leader. Under Pritchard, the school founded programs that were the first of their kind anywhere in the world: veterinary epidemiology, preventive medicine, zoological medicine, neurology, ophthalmology, reproduction, and cardiology. He championed what was then called One Medicine, the idea that animal health and human health are fundamentally connected. That concept evolved into One Health, which the school continues to support through its One Health Institute, founded in 2009. In October 1970, the William R. Pritchard Veterinary Medical Teaching Hospital opened as the first facility in the nation to provide primary, secondary, and tertiary animal care at a veterinary school. Meanwhile, Pritchard spent years fighting Southern California politicians who wanted to establish a rival public veterinary school at UC Irvine, UCLA, UC Riverside, UC San Diego, or Cal Poly Pomona.

For all its academic distinction, the school spent decades in physical squalor. Bond issues for UC facility construction were repeatedly defeated at the polls, and the $23 million promised for a second veterinary building in the campus health sciences complex never materialized. By 1998, the American Veterinary Medical Association was horrified enough by the state of the school's facilities to grant only two years of limited reaccreditation, based on a single damning issue: the buildings were appallingly poor. U.S. News and World Report, which had ranked the school number one in the nation for decades, dropped it from its rankings entirely. The embarrassment finally forced the campus administration to prioritize construction. Modern buildings rose over the following years, and the school completed its migration from aging Haring Hall to the southwest campus health sciences district on March 28, 2017, with the opening of a new Student Services and Administrative Center.

The school's research contributions have reached well beyond the exam room. Its faculty first described simian immunodeficiency virus in monkeys and feline immunodeficiency virus in cats, providing the earliest animal models for AIDS research. In 1989, virologist Tilahun Yilma developed a genetically engineered vaccine for rinderpest, a cattle disease that had caused famine and economic losses exceeding $500 million in a single 1980s African outbreak. Researchers identified mutations in genes DLX5, DLX6, and ADAMTS20 that are associated with cleft palate and cleft lips in both dogs and humans. They discovered that taurine deficiency causes dilated cardiomyopathy in cats and identified the first genetic cause of hypertrophic cardiomyopathy in felines. The school's PREDICT initiative, awarded $175 million by USAID, works to detect emerging infectious diseases in more than 30 countries. With over $70 million in annual research funding, it leads all 30 accredited veterinary schools in the nation.

The school's reach extends into some unexpected places. Under an agreement with the California Department of Fish and Game, its Wildlife Health Center administers the Oiled Wildlife Care Network, operating cleaning and rehabilitation facilities at Cordelia and San Pedro and coordinating 23 partner organizations during oil spill emergencies. The SeaDoc Society, affiliated with the school's Karen C. Drayer Wildlife Health Center, works on marine ecosystem health in the Salish Sea. A satellite campus in San Diego provides specialized hemodialysis and cardiology services to Southern California pets, services that the vast majority of veterinarians cannot offer. A dog named Whiskey, a Munsterlander who lost his jaw to cancer, received a pioneering mandibular reconstruction using a titanium plate seeded with bone growth protein. Over time, his cells proliferated around the plate, forming material that resembled natural bone. It is that kind of place: a school where the boundary between routine care and frontier medicine barely exists.