Sebastiano Ghezzi (1580–1645) was an Italian painter and architect of the Baroque period.
Born in Comunanza near Ascoli Piceno, he traveled to Bologna, where he derived instruction in design from Guercino.
He was named Papal engineer by Pope Urban VIII, and awarded a knighthood of the Cross.
His son Giuseppe was known as a painter; his grandson, Pier Leone, has become known for his ink caricatures.
Sebastiano frescoed the lunettes (1612–1613) in the cloister of S. Domenico in Ascoli, where he left a self-portrait.