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The Sanford School is located in two modern buildings, the Sanford Building and Rubenstein Hall, at the corner of Science Drive and Towerview Road, across from the Duke Law School. Both buildings feature neo-gothic architecture that pays homage to the design of Duke Chapel and the buildings of the main quad.

The 50,000-square-foot Sanford Building, designed by Architectural Resources, Cambridge, opened in 1994. At its core is the Fleishman Commons, a multipurpose space for lectures, meetings, and dining. Staircases framing two sides of the commons feature spaces with couches and benches, providing spontaneous meeting spaces for the Sanford community. The building includes classroom space, the Rhodes Conference room, and offices for several research centers, including the Center for Strategic Philanthropy and Civil Society, the DeWitt-Wallace Center for Media and Democracy, the Hart Leadership Program, and the Heyman Center for Ethics, Public Policy and the Professions.

The 46,000-square-foot Rubenstein Hall opened in August 2005 and houses several Sanford programs, including the graduate program offices, the Duke Center for Child and Family Policy, the Duke Center for International Development, and POLIS, the Center for Political Leadership, Innovation and Service.

The buildings in the Sanford complex are fully equipped for wireless networking.