The river rises below Dowlings Hill, sourced by runoff from the Great Dividing Range, and flows north across the mostly uninhabited coastal plain.

The Esk River enters the Annan Forest Reserve and flows through a wetland dominated by mangroves.

[2] At its mouth, the Esk River is joined by the Annan River and together discharge into Walker Bar and then onto the Coral Sea approximately 7 kilometres (4 mi) south of Cooktown.

[1] Much of the Esk River catchment lies within protected area tenure.

As of 2013[update] the river appeared to be in a healthy condition with limited siltation and only infrequent pockets of erosion.