A Renaissance facade of pale travertine — Pius II wanted a "domus vitrea", a glass house — fronts a tall Gothic-influenced hall church inside, modelled on the German hall churches the pope had admired in Vienna. Five altarpieces, one in each chapel, were commissioned for the opening by the leading Sienese painters of the 1460s: Sano di Pietro, Giovanni di Paolo, Matteo di Giovanni, Lorenzo di Pietro (Vecchietta) and Bartolomeo di Tommaso.
The apse rests on a substructure of vaults built into the hillside that drops sharply into the Val d'Orcia. The whole east end of the church has been sliding gently downhill since 1462 and is held in place by twentieth-century steel.