The church was built between 1236 and 1254 by the Franciscan community. The members of the community arrived in Bologna in 1218 when Bernardo di Quintavalle, one of the first disciples of San Francesco, moved here. San Francesco joined his disciples in Bologna some years later.

At present, the church is a sort of pastiche of different styles including Romanesque, Gothic and Early Renaissance.

The high Gothic-Romanesque  façade, the two bell towers (the biggest one dating back to the early years of the 15th century and the other to 1260), and the arches in the chapels are particularly important. Next to the chapels there are two buildings of the 12th century where Accursio, Odofredo e Rolandino de' Romanzi were buried.

Inside the church, surrounded by an austere and imposing structure, a wonderful marble altar-piece stands out: it was sculpted between 1388 and 1393 by the Venetians Jacobello and Pier Paolo dalle Masegne. Moreover, there are several noteworthy sepulchral monuments such as Pope Alexander V's grave designed by Sperandio (1482), the Romanesque Muzzarelli chapel and the airy cloisters (14th and 15th century) of the nearby convent.