The Sweetwater rises in southwestern Fremont County, at the continental divide near South Pass Wyoming, on the southern end of the Wind River Range.

In southern Natrona County, it passes Devil's Gate and Independence Rock along the Oregon, California and Mormon Trails, and empties into the North Platte as the Sweetwater arm of Pathfinder Reservoir.

These trappers and traders soon established a path for their pack trains along the Sweetwater and eventually cleared a rough wagon trail to the Green River.

Smith reasoned since the Sweetwater flowed east it must eventually run into the Missouri River.

Upon arriving back in a settled area on the Missouri River they bought pack horses (on credit) and retrieved their furs.