It begins in the Waskesiu Hills[2] in Prince Albert National Park and flows generally in a southward direction through boreal forests, glacier-carved hills and valleys,[3] muskeg, and prairie en route to the North Saskatchewan River[4] at the east end of the city of Prince Albert.

Several lakes with recreational amenities such as Namekus, McPhee, Anglin, Emma, Christopher, and Halkett are within its watershed.

From its source, the Spruce River heads south out of the Nimrod Hills dropping over 60 metres (200 ft) in elevation into a valley.

Beartrap Creek[7] flows north into Waskesiu Lake and is part of the Churchill River watershed.

From the portage, Spruce River turns south following a valley towards Anglin Lake and Spruce River Dam at the eastern boundary of Prince Albert National Park and the western boundary of Great Blue Heron Provincial Park.

About one kilometre north-east of the dam along Anglin Lake's eastern shore is a pumphouse that lifts water up eight metres at a maximum rate of .65 m3 (23 cu ft) through a 284 m (932 ft) long pipeline into a 10-kilometre long diversion channel that flows into Emma Lake at its northern end.

At the southern end of Christopher Lake, a partially man-made, partially natural channel called Christopher Creek[16] was constructed that connects with Spruce River farther downstream, south of Little Red River Indian Reserve.

[17] The Spruce River begins in the south-central area of Prince Albert National Park in the Waskesiu Hills.