Colossae had been an important city in the region of Asia Minor prior to the time of Paul. Colossae was built along the Lycus River, which was important for trade in the ancient world. As a result, Colossae became a major trading center. It was located on a main overland trade route between Ephesus approximately 100 miles to the west and the Euphrates about 400 miles to the east. The town had declined in importance by the time the gospel was preached there by Epaphras, who was a convert from Colossae. The growth of two sister cities in the Lycus valley spurred the decline at Colossae. This was probably the least influential city to which any of Paul's surviving letters was addressed.

Epaphras, who later joined Paul in prison at Rome, founded this church in the wake of Paul's ministry at Ephesus. It was in this Roman prison where Paul was given news of strange teachings affecting this church. Paul never visited Colossae.