In 1340 the Battle of Sluys was fought nearby at sea during the Hundred Years' War.

During the Eighty Years' War in 1587 the town was captured by Spanish troops under the Duke of Parma and was retaken in 1604 by a Dutch and English force under Maurice of Nassau.

From 2006 until its closure in 2013, Oud Sluis was one of only two Michelin three-starred restaurants in the entire country.

In addition to the town of Sluis itself, the municipality is made up of the following population centres: Sint Anna ter Muiden, with a population of only 50 (2001), is a small village about 1 km west of the town of Sluis, located on the westernmost point of the Netherlands.

After the opening of the Westerschelde tunnel near Terneuzen in 2003, the ferry now carries only pedestrian and bicycle traffic.