The river flows generally in a north-westerly direction, joined by three minor tributaries that drain waters from the Trevethan Range before finally heading eastwards to Walker Bay.

[9] Being in a wet-dry tropical climate the river receives the majority of its approximately 1,800-millimetre (71 in) rainfall per year between the months of December and April, a period known as the wet season.

[10][11] Towards the end of the 19th century non-Aboriginal peoples had started to colonize the Far North Queensland region, and with the shift from predominantly gold mining activity (especially at Palmer River) to tin, lead, silver and copper mining, they started to move into the Annan River catchment and Kuku Nyungkal country.

Later, the industry had to adapt to exhausted supplies by consolidating and building water channels (races) through the Upper Annan River ranges to access higher, more difficult to reach deposits.

The western and northern parts are more sparsely vegetated consisting of open eucalypt forest and woodland with pockets of rainforest along Oaky Creek.