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It rises in central Klamath County along the north side of Fuego Mountain in the Winema National Forest , approximately 40 mi (64 km) northeast of Klamath Falls. It flows in a large inverted U-shape, first north, through the mountains, then curving westward to flow southwest across the Klamath Marsh . From the southern end of the marsh it flows south past Chiloquin, where it receives the Sprague River from the east. It enters the northern end of Upper Klamath Lake approximately 20 mi (32 km) NNW of Klamath Falls.
In the ranching valley north of Upper Klamath Lake, the river provides irrigation through a network of ditches. The Nature Conservancy has acquired a portion of the delta on Upper Klamath Lake as a habitat for migratory birds.