Constantine completely altered the relationship between the church and the imperial government, thereby beginning a process that eventually made Christianity the official religion of the empire. Many new converts were won, including those who converted only with the hope of advancing their careers. The church was also faced by a new form of governmental interference when Constantine presided at the Council of Nicaea, which addressed the Arian controversy (a debate between Arius and Athanasius and their followers over the nature of the Son of God); the council provided the definition of the relationship between God the Father and God the Son that is still accepted by most Christians today. Although Nicaea spoke against Arianism, which maintained that the Son is a created being and not equal to God the Father, Constantine in later life leaned toward it, and his successor, Constantius II, was openly Arian. Despite this turmoil and the outright hostility toward Christianity of the emperor Julian the Apostate (reigned 361–363), the church survived, and the adherents of the traditional Roman religion relapsed into passive resistance. The quietly mounting pressure against paganism in the 4th century culminated in the decrees of Emperor Theodosius I (reigned 379–395), who made Catholic Christianity the official religion of the empire and who closed many pagan temples. By the end of the 4th century, therefore, Christianity had been transformed from a persecuted sect to the dominant faith of the empire, in the process becoming intertwined with the imperial government.

The link between church and state was expressed in the civil dignity and insignia granted to bishops, who also began to be entrusted with ambassadorial roles. Constantine himself appointed bishops, and he and his successors convened councils of bishops to address important matters of the faith. By 400 the patriarch of Constantinople (to his avowed embarrassment) enjoyed precedence at court before all civil officials. The emperors issued a number of rulings that afforded greater privilege and responsibility to the bishops, enhancing their position in both church and society. The close relations between the empire and the church in the 4th century were reflected in the writings of St. Ambrose (bishop of Milan, 374–397), who used “Roman” and “Christian” almost as synonyms. After Theodosius ordered the massacre of the citizens of Thessalonica, however, Ambrose demanded that the emperor undergo penance, thereby enforcing upon Theodosius submission to the church as its son, not its master.