Waynesburg is a borough in and the county seat of Greene County, Pennsylvania, United States, 60 miles (96 km) southwest of Pittsburgh. The population was 4,184 at the 2000 census.
The region is underlaid with several strata of coking coal, including the Pittsburgh No. 8 seam, the Waynesburg seam and the Sewickley, or Mapletown seam. The area is also rich with coalbed methane, which is currently being developed from the several underlying coal seams as an alternative fuel source. At one time, there were also natural gas and oil deposits in the area. The Marcellus Shale, the largest domestic natural gas reserve, is currently being developed in Waynesburg and throughout Greene County. Early in the twentieth century, four large gas compressing stations and a shovel factory were located in Waynesburg. It is named after General "Mad" Anthony Wayne who served with George Washington in the Revolutionary War.
Waynesburg is home to Waynesburg University and to Greene County Airport.