The highway runs 5 miles (8 km) entirely on the Umatilla Indian Reservation from Interstate 84 to OR 11 near Mission.

OR 331 begins at an interchange with Interstate 84 and U.S. Route 30 on the Umatilla Indian Reservation.

The highway travels north, passing the Wildhorse Resort & Casino and the tribal headquarters to the center of Mission.

The road then crosses a railroad and the Umatilla River before ascending up to a plateau formed by the river and Wildhorse Creek.

OR 331 terminates at an intersection with OR 11, approximately 4 miles (6.4 km) northeast of Pendleton.