The highlight of this repository of artworks that formerly adorned the duomo is undoubtedly Duccio (di Buoninsegna)'s striking Maestà (1308–11), which was painted on both sides as a screen for the high altar. Duccio portrays the Virgin surrounded by angels, saints and prominent contemporary Sienese citizens; the rear panels (sadly incomplete) show scenes from the Passion of Christ. Entry to the Panorama del Facciatone is included in the entry ticket.

Other notable works include a marble tondo of the Madonna and Child with Four Cherubs (1457–59) by Donatello, a stained-glass window (1287–88) by Duccio, a Nativity of the Virgin (1342) by Pietro Lorenzetti and 12 statues of prophets and philosophers by Giovanni Pisano. These statues originally stood on the facade and were designed to be viewed from ground level, which is why they look so distorted as they crane forward.

Entry to the museum and the Panorama del Facciatone is included in the OPA SI and Acropoli passes.