From the 14th century onwards, the Lordship of Derenburg was affected by the conflicts between the Regenstein counts and the Prince-Bishops of Halberstadt. The town became notorious for the Derenburg witch trials conducted in 1555; further witch-hunts continued up to the early 18th century. During the Thirty Years' War, in 1623, Derenburg was devastated by Imperial troops led by Colonel Heinrich von Schlick. With the secularised Principality of Halberstadt, the town became part of the newly established Kingdom of Prussia in 1701.