According to the Acts of the Apostles (Acts 2:9) in the Bible ethnic Jews and converts to Judaism from the Parthian Empire (which included parts of western Afghanistan[24][25][26]) were present at Pentecost. According to Eusebius' record, the apostles Thomas and Bartholomew were assigned to Parthia.[27]

A legend that is contained in the apocryphal Gospel of Thomas and other ancient documents suggests that Saint Thomas preached in Bactria, an ancient region in Central Asia that was located on flat land which straddles modern-day northern Afghanistan.[28] An early third-century Syriac work known as the Acts of Thomas[27] connects the apostle's ministry with two kings, one in the north and the other in the south. According to the Acts, Thomas was at first reluctant to accept this mission, but the Lord appeared to him in a night vision and compelled him to accompany an Indian merchant, Abbanes (or Habban), to his native place in northwest India. There, Thomas found himself in the service of the Indo-Parthian (Southern Afghanistan, Pakistan, and Northern India) King, Gondophares. The Apostle's ministry resulted in many conversions throughout the kingdom, including the king and his brother.[27]

Bardaisan, writing in about 196, speaks of Christians throughout Media, Parthia, and Bactria[29] and, according to Tertullian (c.160–230), there were already a number of bishoprics within the Persian Empire by 220.[30] By the time of the establishment of the Second Persian Empire (AD 226), there were bishops of the Church of the East in northwest India, Afghanistan, and Baluchistan, with laymen and clergy alike engaging in missionary activity.[27]