It is approximately 49 miles (79 km) long[4] and drains an arid farming valley, the Little Lost River Valley, bordered by the Lost River Range on the west and Lemhi Range on the east.

Instead of emptying into a larger body of water, it disappears into the ground at the edge of the Snake River Plain, a phenomenon that gives it its name.

The river flows generally south-southeast receiving many tributaries such as Wet (the largest), Badger, Deer, Uncle Ike, Sands, Cedarville, South, and Hurst creeks.

A few miles past Howe, the river disappears into the earth at about 4,806 feet (1,465 m) above sea level.

The road begins in the community of Howe, at an intersection with SH-33, then runs roughly north-northwest towards the settlement of Clyde.