In the 18th century, the interior of the Cape was wild and dangerous, with Boers clashing with the Khoe-San in the Sneeuberg Range, and the Xhosa to the east around the Great Fish River. Graaff-Reinet was named after former Cape governor Van der Graaff and his wife (whose maiden name was Reinet), and became an outpost in the harsh countryside. It was the fourth district in the Cape Colony to be granted a drostdy – the residence of a landdrost (local official) and seat of local government. This resulted from British attempts to establish law and order; they failed, and the town’s citizens threw out the landdrost and established an independent republic. The British regained a semblance of control soon afterwards, but were constantly harried by both disgruntled Boers and a joint force of Khoe-San and Xhosa warriors.

In the mid-19th century, Graaff-Reinet became an important staging post for Voortrekkers heading north and escaping the control of the Cape Town administration.