The main branch of the John Day River rises in the Strawberry Mountains in eastern Grant County. The North Fork heads on the western slope of the Elkhorn Mountains in northeastern Grant County. The Middle Fork rises near the crest of the Blue Mountains on the eastern edge of Grant County. The South Fork's source is in northern Harney County, about south of the Grant County line. The main, south and middle forks each have their heads in different parts of the Malheur National Forest, while the North Fork's source is located within in the Wallowa-Whitman National Forest. The main fork flows initially north, then west through the John Day Valley and through the cities of Prairie City, John Day and Mount Vernon. At Dayville, in western Grant County, it is joined from the south by the South Fork John Day River, then flows north through Picture Gorge and the Sheep Rock Unit of the John Day Fossil Beds National Monument.