The Umatilla River's headwaters lie in the Blue Mountains at the confluence of its north and south forks in the Umatilla National Forest of northeastern Oregon. Flowing generally west, the river receives Lick Creek and Bear Creek, both from the :wikt:right bank|right before reaching the unincorporated community of Bingham Springs. Further downstream it receives Rock Creek from the right, then Bobsled, Augur, and Ryan creeks from the left before entering the Umatilla Indian Reservation and reaching the unincorporated community of Gibbon. From Gibbon to the river mouth, tracks of the Union Pacific Railroad run parallel to the stream. Between Gibbon and Cayuse, three creeks—Squaw, Buckaroo, and Coonskin—enter the river from the left. Downstream of Cayuse, Moonshine, Cottonwood, and Mission creeks also enter from the left. The river flows by Mission at about river mile 61 or river kilometer 98, leaves the Indian reservation, and reaches the city of Pendleton at about RM 56, passing under Oregon Route 11. Wildhorse Creek enters from the right, then Patawa Creek from the left. The river passes under Interstate 84 and receives McKay Creek from the left. Shortly thereafter, Birch Creek enters from the left about from the mouth. Coombs Creek enters from the left about below that, and then the river, turning north, flows by Echo and under I-84 again. The Umatilla reaches Stanfield about from the mouth, then passes under Oregon Route 207 and receives Butter Creek from the left. Reaching Hermiston at about RM 9, the river flows by a United States Geological Surveystream gauge about from the mouth, then passes under Interstate 82 and Oregon Route 730 before entering the Columbia River at Umatilla. The Umatilla River joins the Columbia at what is called Lake Umatilla, a reservoir formed by the John Day Dam on the Columbia. The confluence is from the Columbia's mouth on the Pacific Ocean at Astoria. McNary Dam, another dam on the Columbia, is slightly upstream at about RM 292.
Fish
The Umatilla River supports populations of spring Chinook, fall Chinook, and Coho salmon as well as small trout in its upper reaches. Public access to salmon and steelhead fishing is fairly good downstream of the Oregon Route 11 bridge. Upstream of the bridge, the river runs through the Umatilla Indian Reservation, where fishing is limited to those with a tribal permit.