Waynesburg is a borough in and the county seat of Greene County, Pennsylvania, United States, located about 50 miles (80 km) south of Pittsburgh. Its population was 4,176 at the 2010 census.
The region around Waynesburg is underlaid with several layers of coking coal, including the Pittsburgh No. 8 seam, the Waynesburg seam, and the Sewickley (Mapletown) seam. The area is also rich with coalbed methane, which is being developed from the underlying Marcellus Shale, the largest domestic natural gas reserve. Early in the 20th century, four large gas compressing stations and a steam shovel factory were located in Waynesburg.
Waynesburg is named for General "Mad" Anthony Wayne, one of the top lieutenants of George Washington during the Revolutionary War (1776–81). The borough is the location of Waynesburg University, and it is served by the Greene County Airport.