Its headwaters is located on the Sunny Mountain in the Kuskokwim Mountains. It flows first northward, then turns west and finally runs in a southwesterly direction to the mouth of the Yukon River at Holy Cross in parallel to this. The headwaters of the Innoko located in Innoko National Wildlife Refuge.
During a gold rush in 1907, prospectors came to the valley of the Innoko and built some mining camps such as Ophir, Cripple and Poorman, however, were soon left again.
The only spot on the river is Shageluk which is mainly inhabited by Deg Xinag.
The current name of the river goes back to the spelling of the Russian Admiralty from 1952. Previously, there had been several names based on the names of Alaska Natives. The former name " Chagelyuk " for the lower reaches of the Innoko found today in Shageluk Slough, a tributary of the Yukon, again.