The river and its 74 tributaries drain about , including the eastern side of the King Range, and flows through Mattole Valley before emptying into the Pacific Ocean. Although the Mattole River's source is at about elevation, its tributaries originate as high as above sea level. The North Fork of the Mattole River enters the river main stem just west of Petrolia. For most of its length, the river is only a east of the King Range National Conservation Area. About halfway to the ocean, near Honeydew, California, the river passes by Humboldt Redwoods State Park. There are numerous tributaries and creeks that feed the drainage area. Some of the largest are the Upper North Fork at Honeydew (as opposed to the North Fork at Petrolia), Honeydew, Bear, Rattlesnake, and Oil Creeks.