The river's main stem begins at the confluence of its east and west forks near Cave Junction in southern Josephine County.

Its drainage basin includes Sucker Creek, which rises in the Red Buttes Wilderness, near Whiskey Peak on the California state line.

The main stem flows generally northwest in a winding course past Kerby and through the Siskiyou National Forest and Kalmiopsis Wilderness.

Changing weather can often result in water levels being too high or too low for safe and successful navigation.

Furthermore, since water levels can rise rapidly, potential bad weather can also be the cause for cancelled or postponed trips.