The Drysdale River flows through Drysdale River National Park in the Kimberley region of Western Australia, making it one of the largest and least accessible national parks in Australia. There is no public road leading to the park, which means access is exclusively by air. Float plane is the standard means of entry and exit, with operators typically landing on a pool a couple of kilometres above Solea Falls. The river can also be reached by flying to Drysdale Station and then transferring overland to the put-in point.

The river offers a variety of paddling conditions, ranging from easy flatwater sections to rapids, and is suited to pack rafting expeditions. Guided commercial trips typically run from late March into April, suggesting this is the preferred season for paddling. Western Australia Parks authorities do not permit entry before 15 June in some years due to prescribed burning requirements, so trip timing must be confirmed with park management well in advance.

Crocodiles are a significant hazard on the Drysdale River and must be taken seriously. At the river's mouth, sandbars extend for several miles and require careful navigation. The river includes notable features such as Solea Falls and Petrogale Falls, both of which are accessible by paddling and walking. The gorges in the upper reaches are described as scenic, and fish are abundant, with reports of fish leaping clear of the water in large numbers.

Guided expeditions on the river typically run for three weeks or more, with bush camping every night. The remoteness of the location means paddlers must be fully self-sufficient. Amphibious aircraft are used for both ingress and egress, and float plane operators have limited landing options, so logistics require careful coordination. The river is rarely visited and rarely promoted, contributing to its wild and uncommercialised character. There are no public facilities for independent paddlers within the park itself, though Drysdale Station near the park boundary offers caravan facilities and fully catered accommodation.