Before the present-day Basilica was constructed, the former estate upon which it sits was once home to a small oratory built by Emperor Constantine I. The Emperor built it over the site on which it tradition held that St. Lawrence was buried in 258. In the 580s, Pope Pelagius II commissioned the construction of a church over the site in honor of the Saint. In the 13th century, Pope Honorius III commissioned the construction of another church in front of the older one. It was adorned with frescos depicting the lives of Saint Lawrence and the first martyred deacon, St. Stephen, who is interred with St. Lawrence in the crypt, or confessio, under the high altar. The two structures were later united during a program of urban renewal. Excavations have revealed several other crypts of various persons, buried below the contemporary street level. Pope St. Hilarius is also buried here.
The portico of circa 1220 has Cosmatesque decoration by the Vassalletto family of craftsmen. The 13th-century frescoes, which were reconstructed, depict scenes from the lives of St. Lawrence and St. Stephen, both being martyred, young deacons. There are two ancient sarcophagi in the portico: a Christian one, possibly decorated in the 7th century on an older sarcophagus, has a relief depicting putti (cherubs) picking grapes. While vines and grapes are symbols of the Holy Eucharist, these images are probably not symbols thereof. Further, two Romanesque stone lions were moved here from the old entrance.
The campanile was built in the 12th century. Immediately inside the entrance is the tomb of Guglielmo Cardinal Fieschi, who died in 1256, but was entombed in an ancient sarcophagus, itself being incidentally carved with a relief depicting a pagan marital feast.
Inside, the choir enclosure and pulpit have Cosmatesque decoration, and there is also a fine Cosmatesque Paschal candlestick from the 12th or 13th century. The antique Ionic capital on the column directly behind the pulpit has carvings of a frog and a lizard. On the triumphal arch are Byzantine mosaics from the 6th century, depicting Christ with saints. The confessio below the high altar is entered from the nave. Here, St. Lawrence and St. Stephen are enshrined. The latter was transferred from Constantinople by Pope Pelagius II during his restoration of the Basilica. Behind the high altar is a Papal altar with an inscription of the names of the makers, namely the Cosmati family, and dating it to 1148.
The Basilica was home to the Latin Patriarch of Jerusalem from 1374 to 1847. In 1943 the Basilica was bombed during the Second World War. Restoration continued until 1948, allowing some accretions from the 19th century to be removed. However, the frescoes on the facade were destroyed.
The Basilica adjoins a major cemetery, and therefore holds a large number of funerals.