The church is dedicated to Pope Sixtus II and houses his relics (transferred there from the Catacomb of Callixtus in the sixth century.)

San Sisto was rebuilt in the early 13th century by Pope Innocent III.

In 1219 Honorius then invited Dominic and his companions to take up permanent residence at the ancient Roman basilica of Santa Sabina, which they did in the early 1220.

After that they founded a convent and studium on June 5, 1222, thus forming the original studium of the Dominican Order in Rome, out of which the 16th-century College of Saint Thomas at Santa Maria sopra Minerva and the Pontifical University of Saint Thomas Aquinas (Angelicum) would grow.[relevant?

][1] Dominican nuns still occupy the monastery at San Sisto Vecchio.