Leatherwood Creek is a stream in Iron and Madison County in the U.S. state of Missouri. It is a tributary of St. Francis River.
The stream headwaters arise in southeastern Iron County and it flows southeast into western Madison County parallel to Missouri Route C past the community of Jewett to its confluence with the St. Francis about four miles southwest of Rock Pile Mountain.
The source area is at and the confluence is at .
Leatherwood Creek was named for leatherwood near its course.