The School of Veterinary Medicine was established in 1978, opened in 1979, and graduated its first class in 1983. Established through the advocacy of President Jean Mayer, the school was unique in its affiliation to a health sciences complex rather than to a school of agriculture. The school is located on a 634 acre campus in Grafton, Massachusetts, site of a former state mental hospital. The school also shares facilities with the medical and dental schools on the downtown Boston campus, where vet students receive their first year of instruction in the basic sciences. Students at the veterinary school are exposed to care of all types of animals including food (cattle, sheep, swine, goat), fiber (sheep, llama), companion (dog, cat), and sporting (horse) animals. In addition, students are given the option of learning about care for wildlife through the wildlife medicine program. In addition to medicine, surgery, preventive medicine, and public health, the school also educates students about ethics, conservation medicine, and human-animal relationships.

Initial discussions on the establishment of a veterinary school were begun in the early 1970s as the absence of such a school in the New England region combined with a prediction of a nationwide deficit of veterinarians made the need apparent. After a variety of options were explored, including locating a school at the Otis Air Force base on Cape Cod, Tufts, under Jean Mayer's leadership, stepped forward to take the lead in the project. Richard B. Talbot, dean of the College of Veterinary Medicine at Virginia Polytechnic Institute and State University was brought in as interim dean to oversee the startup of the school on a part-time basis. On April 29, 1978, the trustees voted to establish the school as part of Mayer's vision of an integrated "one medicine" program embracing the totality of medical, dental, veterinary, and nutrition education.

The school provides clinical facilities as part of the Tufts-New England Veterinary Medical Center, which includes the Foster Hospital for Small Animals, the Large Animal Hospital, the Cornelius Thibeault Equine Clinic, the Amelia Peabody Pavilion, the Issam Fares Equine Sports Medicine Program, the Harrington Oncology Program, and the Wildlife Clinic at Grafton, as well as the Marine Biological Laboratory at Woods Hole, and the Ambulatory Farm Clinic based at Woodstock, Connecticut.

The degree of Doctor of Veterinary Medicine (D.V.M.) is the primary degree offered by the school, though since 1995 the school also offers a Master of Science (M.S.) in Animals and Public Policy. The school features several signature programs which offer specialized perspectives on veterinary sciences, including Wildlife Medicine, Equine Sports Medicine, International Veterinary Medicine, Ethics and Values in Veterinary Medicine, and Biotechnology and Veterinary Medicine.