Sixteen Mile Creek rises in the Lewis and Clark National Forest in the Crazy Mountains in southeastern Meagher County.

It flows generally west, south of the Big Belt Mountains, and southwest, past Maudlow and joins the Missouri 6 miles (9.7 km) southeast of Toston, at the site of the ghost town of Lombard.

Sixteen Mile Creek is one of the more historically important areas in Montana.

Its name derives from the fact that it enters the Missouri River 16 miles (26 km) downstream from Three Forks, Montana.

The rail bed of the original Montana Railroad runs through this creek canyon, which includes some really outstanding scenery.