The foundation of the church is dated around the VII century, on orders of Pope Leone II, that dedicates it to San Sebastiano and San Giorgio. It possible if not probable that the building works used pre-existent masonry, perhaps from a civil building and a deaconate.
The plan itself, quite irregular, is a testimony of a place grow into several add-ons and transformations throughout time. Pope Zaccaria (741-752), of Greek origins, transfers from Cappadocia the remnants of San Giorgio’s head and gives them to the church, that at the time was the center of a part of the city attended by public officials, merchants and byzantine soldiers. During IX century, under Gregorio IV pontificate, consistent works of restoration changed the way the building looked.
Around half of the XIII century the construction of the portico is completed, a gift from prior Stefano di Stella. A beautiful inscription on the trabeation, in gothic language, marks the moment. Probably in the same period the bell tower is built.
Between the end of the 12th century and the beginning of the 13th, the fresco in the apse is donated from Cardinal Giacomo Gaetano, attributed to Cavallini or his scholars.
Other interventions occurred during 15th and 16th centuries, while between 1665 and 1669, under the pontificate of Clemente IX, the portico got completely restored and changed from a single cover scheme to a triple cover one.
During the 18th century, after a period of decadence and deterioration, the church undergoes consistent consolidation works and another restoration (under pontificate of Leone XII, Gregorio XVI and PIO IX). During this period the façade is partially reconstructed, raised and coated with a fine plaster (1824-25). The left side walls got strengthened, the bell tower is consolidated and general works to correct humidity problems took place.
Between 1923 and 1926 the church goes again under intense restoration by the superintendence to Rome’s monuments, under Antonio Mufioz’s direction. The main object of the restoration is to return the church to its medieval splendor, clearing it from the add-on of the following historical periods.
This restoration brought back the old windows that lit up the aisle got restored, and the original floor got back to the original height. The apse got restored completely and got marble panel covering; during this period workers found several residues of columns thought to be proof of the existence of an ancient schola cantorum (singing school) dated back to Pope Gregorio IV pontificate (VIII-IX century). This pieces are now part of the internal walls of the church.
A new round of restorations took place in 1963 under the supervision of the Superintendence. Just before the attack in 1993, the superintendence had just finished restoring the roof over the right side aisle, that withstood most of the destructive power of the blast, helping preserve the inside of the church almost intact.