The villages of Portage Creek, Ekwok, Koliganek and New Stuyahok are on the river.

Five species of Pacific salmon (Chinook, coho, sockeye, chum, and pink) spawn in the river or its tributaries.

Most notable is the annual run of king (Chinook) salmon which occurs from mid-June to mid-July.

Rainbow trout, northern pike, grayling, burbot, whitefish and Arctic char are also present in the Nushagak.

It is estimated that over 50% of the world's production of wild salmon is harvested in the Nushagak River and the Bristol Bay area.