The Firehole River starts and ends in Yellowstone National Park. It starts near Madison Lake, a small lake west of Shoshone Lake, and flows through the park 21 miles to Madison Junction. There it merges with the Gibbon River to form the Madison River.

Along this course, the river flows through many hydrothermal areas: Lone Star Geyser Basin, Upper Geyser Basin, Midway Geyser Basin, and the Lower Geyser Basin. Because of this, it receives geothermally heated water, which means this river is warmer than many other rivers in the park.