It gives the name to the settlement of Prophet River, British Columbia, as well as the Prophet Formation, a stratigraphic unit of the Western Canadian Sedimentary Basin.

The headwaters of the Prophet River can be found in the Bruce Ridge of the Muskwa Ranges in the Northern Rockies, at an elevation of 2,000 meters (6,600 ft).

It flows eastwards between the Northern Rocky Mountains Provincial Park and the Redfern-Keily Provincial Park, with occasional waterfalls on its course.

North of Klingzut Mountain it receives the Besa River just before flowing from the mountains into the plains The Milliken Creek and Bat Creek flow into the Prophet River east of the Rocky Mountains.

It then flows into the Muskwa River immediately west of Fort Nelson, at an elevation of 304 meters (997 ft).