The basilica is dedicated to St. Lawrence of Rome, deacon and martyr. The name "Lucina" derives from that of the Roman matron of the AD 4th century who permitted Christians to erect a church on the site. Pope Marcellus I supposedly hid on the site during the persecutions of Roman Emperor Maxentius, and Pope Damasus I was elected there in AD 366. Pope Sixtus III consecrated a church on the site in 440 AD. The church was denominated the Titulus Lucinae, and is so mentioned in the acts of the synod of AD 499 of Pope Symmachus. The church was first reconstructed by Pope Paschal II in the early 12th century.
The church was consecrated by Pope Celestine III on 26 May 1196.