[3] The river flows northeast from the Kuskokwim Mountains through Nowitna National Wildlife Refuge and enters the larger river 38 miles (61 km) northeast of Ruby[3] and southwest of Tanana.

[5] In 1980, the 225 miles (362 km) of the river within the wildlife refuge were designated "wild" and added to the National Wild and Scenic Rivers System.

[6] The designation means that most of the Nowitna is unpolluted, free-flowing, and generally inaccessible except by trail.

This segment includes Class II (medium) rapids.

Navigating can be difficult at times because of upriver winds, especially on the lower reaches.