The Basilica of Santa Maria Maggiore was built in the 4th century by order of Pope Liberius on the site of a pagan temple, preserving the original early Christian structure. According to legend, the Virgin Mary appeared to the Pope, giving him instructions for building the church, and a miracle indicated the location. The following day, August 5th, an unusual snowfall whitened a stretch of the Esquiline Hill: here Pope Liberius traced the perimeter of the new basilica in the snow, and construction work began. In 432, the basilica was rebuilt by Pope Sixtus III, who dedicated it to the cult of the Virgin Mary, recognized by the Council of Ephesus in 431.

The basilica displays a mix of architectural styles from different eras. From the medieval period, it retains the Cosmatesque floor, renovated by Ferdinando Fuga in the 12th century during the pontificate of Pope Eugene III, while the splendid mosaics in the apse were created by Jacopo Torriti under the pontificate of Nicholas IV. The Romanesque bell tower, built in 1375 and 75 meters tall, is the tallest in Rome. It houses five ancient bells: the largest bell is called "La Sperduta," cast in 1289. Its ringing, which occurs shortly after 9:00 p.m., is linked to a 16th-century legend that tells of a shepherdess who got lost while tending her flock. As evening fell, the basilica's bells were rung to show her the way home. The shepherdess never returned, but the bells continue to call her.

The Renaissance coffered ceiling dates back to the time of Pope Alexander VI Borgia (1492-1503) and, according to tradition, was gilded with the first shipment of gold from the Americas, a gift from Isabella of Spain.
Toward the end of the 16th century, the two large side chapels were built: the Sistine Chapel and the Pauline Chapel, commissioned by Pope Sixtus V and Pope Paul V, respectively. The Pauline (or Borghese) Chapel houses Rome's most important Marian icon: the Madonna Salus Populi Romani. According to tradition, the image was painted by Saint Luke, brought to Rome under Pope Sixtus III (432-440), and donated to the basilica built by Pope Liberius. The basilica preserves the relic of the Holy Cradle: five sycamore wood slats, part of the manger in which the Baby Jesus was laid, kept in a cradle-shaped reliquary designed by Giuseppe Valadier in 1802.

Between 1670 and 1676, Carlo Rainaldi redesigned the apse into its current form. On the walls of the central nave, above the entablature, mosaic panels dating back to the 5th century are visible. The triumphal arch is decorated with mosaics depicting stories of Jesus' childhood dating back to the time of Sixtus III. In the apse, the splendid mosaic was executed and signed by Jacopo Torriti at the end of the 13th century.