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Construction began on the College of Veterinary Medicine in 1979 and was finished three years later. At the time the Main Building opened, the School of Veterinary Medicine had emerged as a full program at NC State. Soon after, the North Carolina Veterinary Medical Association began a fund-raising campaign in which halls, laboratories, offices, and other areas were assigned values for possible contributions towards construction. The School of Veterinary Medicine Committee and the Building and Property Committee planned, funded, and built the school. The Main Building emerged as one of the most sophisticated and architecturally distinctive facilities on the campus of NC State.

Located on Hillsborought Street near the NC State Fairgrounds, the College of Veterinary Medicine was built on what had originally been the University Dairy Farm. When the farm was relocated, many of the existing barns and other facilities were renovated for animals kept on the site. These animals can easily be brought from the pasture to a courtyard in front of Main Building for students to observe. The courtyard is created from the separation of the building into units, which allow circulation in a mini, academic city of sorts. Designed with a library on one end and food services on the other, Main Building places most of the circulation in a three-story mall. Offices and laboratories open out to this area and, in some cases, allow students to observe activities, such as surgery, through glass walls. The building also features large lecture halls and a stair tower.