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Waynesburg is a borough in and the county seat of Greene County, Pennsylvania, United States, about 50 mile (80 km) south of Pittsburgh. Its population was 4,006 at the 2020 census. Its passenger service ended in 1929, and conversion to 4ft8.5in followed in 1944 as a wartime measure. Then the railroad was renamed the Waynesburg Secondary Railroad. Regular freight service ended on this line in 1976, though part of it still serves (irregularly) for railroad access to a coal mine. The Waynesburg Historic District, Hanna Hall at the university, and Miller Hall are listed on the National Register of Historic Places.

Waynesburg is located northeast of the center of Greene County at (39.897403, 80.185597). Its southern boundary follows the South Fork of Tenmile Creek, an east flowing tributary of the Monongahela River. The borough is surrounded by Franklin Township, a separate municipality. U. S. Route 19 passes through the center of the borough as High Street (westbound) and Greene Street (eastbound), turning on the north side of town to follow Morris Street (northbound) and Richhill Street (southbound). Pennsylvania Route 21 joins US 19 through downtown Waynesburg on High and Greene streets. PA 21 leads east 2 mile (3 km) to Interstate 79 at Exit 14 and continues east another 25 mile (40 km) to Uniontown. To the west PA 21 leads 6 mile (10 km) to Rogersville and 24 mile (39 km) to the West Virginia border. I 79 leads north from Exit 14 21 mile (34 km) to Washington and 53 mile (85 km) to Pittsburgh, while Morgantown, West Virginia, is 24 mile (39 km) to the south. According to the United States Census Bureau, Waynesburg has a total area of , all land.

Its school district is Central Greene School District. The Eva K. Bowlby Public Library is on Bowlby Street (originally named North Richill Street), in the former Bowlby family home. It was bequeathed by Mrs Bowlby, a prominent local citizen who died in 1957, to serve as a children's library.