Leatherwood Creek is a tributary of Wills Creek, long, in eastern Ohio in the United States. Via Wills Creek and the Muskingum and Ohio rivers, it is part of the watershed of the Mississippi River, draining an area of on the unglaciated portion of the Allegheny Plateau.
Leatherwood Creek rises just outside the western boundary of the village of Barnesville in Warren Township in Belmont County and flows generally westward, first through a small portion of northeastern Beaver Township in Noble County, and into Guernsey County where it flows through Millwood, Richland, Wills, Center, and Cambridge townships, and through the villages of Quaker City, Salesville, and Lore City. It flows into Wills Creek in the southern part of the city of Cambridge.
Leatherwood Creek was named for the leatherwood which grew along its course.
At the United States Geological Survey's stream gauge near the community of Kipling, the annual mean flow of the creek between 2000 and 2011 was . The highest recorded flow during the period was on September 18, 2004. A reading of no flow was recorded on September 2, 2003.