Situated on the sloping terrain above the ancient forums of Rome, near the present Via Cavour, by the 14th century, a convent associated with the Clarissan order was located at or near the site.

When these nuns abandoned the site to move to San Lorenzo in Panisperna, a frescoed 15th-century image of the Virgin and child with Saints Lawrence and Stephen was uncovered at their former monastery in 1580.

Soon the icon was celebrated as miraculous, and became an object of popular veneration, and led Pope Gregory XIII to sponsor the construction of this church.

In each of the eight sections of the dome are scenes from the life of the Blessed Virgin by several artists, while in the vault and the arches of the chapels are stucco angels by Ambrogio Buonvicino.

In the third chapel on the left, is a Nativity by Girolamo Muziano, flanked by an Adoration of the Magi and Dream of St John both by Cesare Nebbia.

Vincent Pallotti, founder of the Union of Catholic Apostolate in 1835, was devoted to the Madonna dei Monti and to Benedict Joseph Labre, buried in the church.

Cardinal Vicenzo Pecci, later Pope Leo XIII, donated family money in 1856 to members of the Society of Saint Vincent de Paul who tended the sick poor at the church.