The Nowitna River is a 250-mile (400 km) tributary of the Yukon River in the U.S. state of Alaska. 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 and southwest of Tanana. Major tributaries include the Titna, Big Mud, Little Mud, Lost, and Sulatna rivers.