This basilica was constructed on the Arx, one of the peaks of the Capitoline Hill. Legend has it that it was here that the Virgin Mary appeared to Octavius before he became Emperor Augustus. The church took the place of the ancient and very important Temple of Juno Moneta.

The early basilica was much like the present building's transept. It was constructed in the 13th century for the Franciscans, probably following the design of the great architect Arnolfo di Cambio. There is a very steep flight of 124 steps going up to the church, built by the city authorities in 1348 as a votive offering to the Virgin Mary in hope of stamping out the Black Death that was convulsing Europe.
At the same time, the church's orientation was changed: its axis was now parallel with that of the Vatican, and no longer with that of the Palazzo dei Conservatori. The tribune of Rome, Cola di Rienzo, was the first to climb these steps.
In 1564, Pope Pius IV had the medieval apse destroyed along with its frescos, painted by that great late 13th century Roman, Pietro Cavallini. The church itself was deconsecrated during the Napoleonic occupation and transformed into a stable. The monastery to which the church was originally attached was pulled down when the Vittoriano was constructed.