The cult of St Theodore was prominent and widespread by the end of the 4th century and a mosaic including Theodore was erected at SS Cosmas and Damian c. 530. San Teodoro may have been built as early as the 6th century as well.[4] Its apsis mosaic dates to the 6th century and shows Christ in a black robe with gold lati clavi,[2] which on Roman garments indicated high rank, seated on an orb representing the heavens and flanked by Peter and Paul and by the two martyrs Theodore (a later addition, from Nicholas V's restoration) and Cleonicus.
The church is also traditionally one of the seven original deaconries in Rome, being assigned to a deacon by Pope Agatho (c. 678), though the first titular deacon known by name was Roberto, who lived around 1073 and died before 1099.
Its titulus was reestablished on 2 December 1959 by Pope John XXIII, with William Theodore Heard (1959–1970, pro hac vice presbyterial titular 1970–1973). The last titular of the church was Vincenzo Fagiolo, who died on 22 September 2000.
At the back of the atrium, outside the church, is an ossuary with stacked skulls and bones, visible through a grille. The Capitoline Wolf was kept in this church until the 16th century. As a Greek Orthodox church, it now has an iconostasis, or icon screen, that separates the sanctuary from the main body of the church.