Mining, boatbuilding and hunting/fishing have been important to the area for hundreds of years. From 1730 onwards there was a Sami market here. Eventually Norwegians settled here and established trading connections with the Swedes. Many of the original trade routes are now hiking paths.

Mo i Rana grew as an industrial centre in the early 20th century and people moved from all over Norway to work here. The Iron Mill was one of the biggest employers in the area. 

Andenes was an important fishing village during the Iron Age. In the Middle Ages, Germans and the Dutch regularly came to Andenes to buy dried fish. The fishermen here also came into contact with the Hansa. By the late 19^th century, Andenes had significantly greater exports of fish than any other region in Vesterålen. The stretch between Andenes and Senja is one of the most fish-rich stretches of sea in Europe.

By the early 1900s, it had become one of the largest fishing ports in Norway. The Andøya Air Station was built here in the 1950s and was largely funded by NATO. At its peak, in the 1980s, Andenes was the largest village in the traditional region of Vesterålen. However, when the Andøya Air Station shut down the population dropped significantly.