San Francesco is a basilica church erected in c. 1228-1255 and later enlarged in the 14th-15th centuries, the original Romanesque edifice being turned into the current large Gothic one.

The basilica is on a Egyptian Cross plan, with a nave covered by spans and a transept, according to type favoured by the Mendicant Orders, which needed spaces capable to house large crowds of faithful.
The current interior looks rather sober after a fire in 1655 and the restoration of 1885-1892, when much of the Baroque altars were demolished (part of the paintings has been however returned in recent times). The hut-shaped, neo-Gothic façade, flanked by the 1763 campanile, dates to the early 20th century. The medieval marble decoration and the 15th century portal were removed in that occasion.

The counterfaçade houses the remains of two 14th century sepulchres, as well as two large fragmentary frescoes from the former city gates of Porta Romana and Porta Pispini: an Incoronation of the Virgin by Sassetta and Sano di Pietro (1447–1450) and a Nativity by Il Sodoma (1531). Also visible is the ancient 15th century portal by Francesco di Giorgio Martini.
Amongst the numerous artworks in the church, are Madonna with Child and Saints by Jacopo Zucchi, an expressive Crucifixion by Pietro Lorenzetti and a fresco by his brother Ambrogio, a Prayer of St. James by Giuseppe Nicola Nasini, a Martyrdom of St. Martina by Pietro da Cortona and a Madonna with Child frescoed by Jacopo di Mino del Pellicciaio.
In the right transept is a 14th-century marble of St. Francis, from the ancient façade.