The river rises in Billerbeck, near the German city of Münster in North Rhine-Westphalia, and crosses the border with the Netherlands near Vreden (Germany) and Rekken (Netherlands). From there, it flows through the province of Gelderland to join the IJssel at Zutphen after about 110 kilometres.
Before the coming of the railway, the Berkel was a major shipping route for goods from Münster to Eibergen, Borculo, and Zutphen, transported in flat-bottomed boats called Berkelzompen. In the 1950s, the Dutch stretch of the river was channelized to prevent flooding and to improve drainage. Recently old bends have been reconnected to the straightened lengths of the river.
Towns along the course of the Berkel include:
- in Germany: Billerbeck, Coesfeld, Gescher, Stadtlohn, Vreden
- in the Netherlands: Eibergen, Borculo, Lochem, Almen, Warnsveld, Zutphen