The headwaters of the Wickham River are situated on an area of rugged stony hills and a sandstone plateau[3] as the river rises on the southeastern slopes of Mt Kimon.

It flows generally northeast, joined by seven tributaries including the Humbert River, Soda Springs Creek, Depot Creek and Broadarrow Creek and through one permanent waterhole, Johnston Billabong, before reaching its confluence with the Victoria River, south of the Fitzgerald Range near Pompey Knob.

[2] The Judbarra / Gregory National Park was established in 1981 encompassing much of the catchment.

During the dry season, a string of waterholes form along the course of the river some of which are spring-fed and almost permanent.

[4] The area surrounding the Wickham River are the traditional lands of the Aboriginal community of Yarralin, also known as Walangeri.