Paint Creek is a tributary of the Scioto River, 94.7 mi (152.5 km) long, in south-central Ohio in the United States. Via the Scioto and Ohio Rivers, it is part of the watershed of the Mississippi River. It drains an area of 1,143 mi² (2960 km²).
Paint Creek rises in southwestern Madison County and flows initially south-southeastwardly through Fayette County and along the boundaries of Highland and Ross Counties, past the towns of Washington Court House and Greenfield. Downstream of Greenfield, a dam causes the stream to form Paint Creek Lake, which is the site of Paint Creek State Park. Below the dam, Paint Creek flows eastwardly through Ross County, past Bainbridge and just to the south of Chillicothe to its confluence with the Scioto River.