Its main façade was completed in 1380 with a nave oriented northeast–southwest. A proposed expansion of the eastern transept would have transformed the church into an ambitiously massive basilica, the largest then in the world, with an east–west nave. However, the scarcity of funds, in part due to war and the Black Death, truncated the project. Two walls of this expanded eastern transept remain; through an internal staircase, visitors can climb for a grand view of the city.

The Siena Cathedral Pulpit is an octagonal 13th-century masterpiece sculpted by Nicola Pisano with lion pedestals and biblical bas-relief panels. The inlaid marble mosaic floor of the cathedral, designed and laboured on by many artists, is among the most elaborate in Italy. The Sacristy and Piccolomini library have well-preserved Renaissance frescos by Ghirlandaio and Pinturicchio respectively.

Other sculptors active in the church and in the subterranean baptistry are Donatello, Lorenzo Ghiberti, Jacopo della Quercia and others. The Museo dell’Opera del Duomo contains Duccio’s famous Maestà (1308–11) and various other works by Sienese masters. More Sienese paintings are to be found in the Pinacoteca, e.g. 13th-century works by Dietisalvi di Speme.