The river's source is at Big Springs and the Henrys Lake outlet (10 miles northwest of Big Springs). To the east is Targhee Pass, with Raynolds Pass to the northwest and Red Rock Pass to the southwest. The headwaters of the Henrys Fork are within of the headwaters of the Missouri River (on the Red Rock River and Madison River), located across the continental divide in Montana. Henry's Fork drains the northeastern corner of the Snake River Plain, along the continental divide.