The forest encompasses a mountainous area consisting of the Kettle River and Selkirk mountain ranges, and the upper reaches of the Columbia River.

The forest has a total area of 1.5 million acres. A 1993 Forest Service study estimated that the extent of old growth in the Forest was 212,488 acres (85,991 ha). In descending order of forestland area it is located in parts of Ferry, Pend Oreille, Okanogan, Stevens counties. The forest headquarters is located in Colville, Washington. There are local ranger district offices located in Kettle Falls, Metaline Falls, Newport, Republic, and Tonasket. Most of the Salmo-Priest Wilderness lies within the forest, while its southeastern portion extends into Kaniksu National Forest. With the inclusion of the Tonasket Ranger District, portions of the Pasayten Wilderness are within the forest.

Wildlife include grizzly and black bears, wolf packs, bighorn sheep, cougars, bald eagles, Canada lynx, moose, beavers, loons, and up until recently, the last remaining herd of caribou in the lower 48 US states.