Sansepolcro, formerly Borgo Santo Sepolcro, is a town and comune in Tuscany, Italy, in the province of Arezzo.

Situated on the upper reaches of the Tiber river, the town is the birthplace of the painters Piero della Francesca, Raffaellino del Colle (a pupil of Raphael), Santi di Tito, and Angiolo Tricca. It was also the birthplace of the Italian mathematician Luca Pacioli, and of Matteo Cioni, who translated into Latin Piero della Francesca's treatise about perspective in painting (De Prospectiva Pingendi).