There may have been several cities with the name Derbe, since Derbe (meaning narrow gate or entrance) is mostly a geographical toponym (e.g. Derbent).

The Bible mention Derbe as being nearby Iconium city. When the citizens of Iconium or of Lystra almost killed Paul, Paul managed to escape to Derbe.

Strabo places Derbe on the sides of Isauria, and almost in Cappadocia. Elsewhere, he says it was in the eleventh praefecture of Cappadocia. When the apostles Paul and Barnabas visited Derbe, it was in Lycaonia.

In 1956, on the basis of an inscription dating to 157 BC, Michael Ballance fixed the site of Derbe at a mound known as Kerti Hüyük, some 15 miles (24 km) northeast of Karaman (ancient Laranda), near Ekinözü village in modern-day Turkey. Although subject to controversy, this is considered the most likely site.

Probably sometime prior to the winter of 47-48 C.E., during his first missionary journey, Paul arrived at Derbe after a severe stoning at nearby Lystra. At Derbe, he and Barnabas 'declared the good news' and made "quite a few disciples," including, possibly, "Gaius of Derbe," who is later mentioned as a traveling companion of the apostle. While secular history indicates that after 41 C.E. Derbe was the easternmost city of the political province of Galatia, Luke's description of it in this account as a 'city of Lycaonia' is apparently in a regional or ethnographic sense.

A number of months later, after the Jerusalem council concerning circumcision (c. 49 C.E.), and while on his second tour, Paul returned to Derbe. Though not singled out by name, Derbe may also have been a stop on Paul's third tour when he strengthened the disciples in "the country of Galatia." There is no record of Paul's meeting physical resistance at Derbe, and he makes no mention of the city many years later when recounting his sufferings at other places in its vicinity.

Derbe was included in Paul's letter addressed "to the congregations of Galatia."