The ancient Pons Aurelius was erected on the Tiber River in the third century AD and had collapsed into partial ruin in 772. The Romans had taken to simply calling the bridge "ponte rotto" (broken bridge). Cardinal Francesco della Rovere lived near these ancient ruins, and lamented that he needed to cross the Tiber on the distant Ponte Sant'Angelo to go to the Vatican, rather than make use of a nearby bridge, and intended to rebuild this old bridge should he ever be elected Pope. Within two years of his election to the papacy in 1471, taking the name Sixtus IV, he realized this intention and commissioned the architect Baccio Pontelli to undertake the project.

The first stone for the new bridge was laid at a ceremony on April 29, 1473, during which two examples of this medal in gold were placed in the foundation. Reusing the foundation of the ancient bridge, work progressed swiftly such that the new bridge, now called the Ponte Sisto, was in passable condition by the time of the Holy Year of 1475. Before its construction, there were only two bridges in the region, and the Ponte Sisto was the first bridge constructed over the Tiber since antiquity. The new bridge would also help to avoid a tragedy similar to what had occurred during the previous Holy Year. On December 18, 1450, a bucking mule caused panic amongst a crowd crossing the Ponte Sant'Angelo. More than one hundred pilgrims were crushed and another two hundred fell into the Tiber and drowned. Construction on the bridge was completed by 1479.