A prosperous trading city on the River Orontes, in the north of the Roman province of Syria, with a substantial and tolerated Jewish population. After the execution of Stephen, Christians arrived from Jerusalem to begin missionary work (Acts 11: 19–20). Hellenists from Cyprus and Cyrene admitted Gentiles to the Church without undergoing the rite of circumcision, and Barnabas, himself a Cypriot, was dispatched to control developments. But so far from holding the line, Barnabas brought in Paul (Acts 11: 22–6). Their liberal policies brought them under suspicion and in 49 CE Paul and Barnabas met the Jerusalem leaders and (according to Acts) a compromise was thrashed out (Acts 15: 1–19); but when Peter later visited Antioch he went back on the agreement and withdrew from sharing a meal with Gentiles (Gal. 2: 11–21). Paul soon left Antioch, travelling now without Barnabas, who had supported Peter. After the fall of Jerusalem (70 CE) there is no certain information about the Church in Antioch, but it is a reasonable supposition that the gospel of Matthew was compiled there or nearby. This gospel represents both a recognition of the Jewish roots of the Church, containing much typically Jewish ethical instruction, but also a firm commitment to the Gentile mission. The savage attacks on the Pharisees, especially in ch. 23, suggest that the separation of Matthew's community from the synagogue is fairly recent. The Christian community is having to justify itself against a renascent Judaism. Matthew has the story of the pagan astrologers visiting the infant Jesus (Matt. 2) and at the end (Matt. 28: 19) he has the risen Christ authorizing the universal mission. In 107 CE Ignatius of Antioch provides evidence that the Church there had acquired a clear structure with a leadership unified in the person of a presiding bishop.

Antioch of Pisidia, on the border of Pamphylia in modern Turkey, was made a colony by the emperor Augustus. It was celebrated for the worship of the Phrygian moon-god, but the Romans suppressed the cult. There was a Jewish group in the city, which Paul and Barnabas visited (Acts 13: 14–52; 14: 19–21), but an initial welcome was followed by a campaign of persecution and their expulsion.