In the Synoptic Gospels (Matthew, Mark, and Luke), Peter and Andrew—whose Greek name means “Manly”—were called from their fishing by Jesus (Jesus Christ) to follow him, promising that he would make them fishers of men. With Saints Peter, James, and John, Andrew asked Jesus on the Mount of Olives for signs of the earth's end, which inspired the eschatological discourse in Mark 13. In John's Gospel he is the first Apostle named, and he was a disciple of St. John the Baptist before Jesus' call.

Early Byzantine tradition (dependent on John 1:40) calls Andrew protokletos, “first called.” Early church legends recount his missionary activity in the area about the Black Sea. Apocryphal writings centred on him include the Acts of Andrew, Acts of Andrew and Matthias, and Acts of Peter and Andrew. A 4th-century account reports his death by crucifixion, and late medieval accretions describe the cross as X-shaped. He is iconographically represented with an X-shaped cross (like that depicted on the Scottish flag).

St. Jerome records that Andrew's relics were taken from Patras (modern Pátrai) to Constantinople (modern Istanbul) by command of the Roman emperor Constantius II in 357. From there the body was taken to Amalfi, Italy (Church of Sant' Andrea), in 1208, and in the 15th century the head was taken to Rome (St. Peter's, Vatican City). In September 1964 Pope Paul VI returned Andrew's head to Pátrai as a gesture of goodwill toward the separated Christians of Greece.