[2] It rises in west central North Dakota, in the Killdeer Mountains in Dunn County.
It joins the Missouri north of Stanton, at the Knife River Indian Villages National Historic Site.
Much of the terrain surrounding the river valley still remains in native grasslands, supporting many species of wildlife, including Whitetail Deer, Mule Deer, Coyote, Fox, Native Grouse, Pheasant, etc.
Many of the small tributaries such as the Little Knife support local farms and ranches; some have been family owned for over 100 years.
The river consistently floods after spring melting (frequently as high as 10,000 cfs) but is two to three magnitudes lower during the summer months.