From Friedrichshöhe to Mägdesprung in the borough of Harzgerode, it is accompanied by the Selke Valley Railway for a distance of 17 kilometres (11 mi).

The Selke has cut deeply into the Harz Mountains in some places whilst in others it runs in a broad valley, depending on the bedrock.

In Meisdorf on the northeastern edge of the Lower Harz, the Selke leaves the forested mountain region and winds across a cultivated plain, continuing to flow in an easterly or northeasterly direction as far as Ermsleben.

Beyond Ermsleben the river swings through 90° to the northwest and runs from here in an almost straight line to its mouth on the Bode near Rodersdorf [de; nl], a village in the borough of Wegeleben.

High above the Selke Valley is a striking and largely preserved medieval castle, Falkenstein, which is open to the public.