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).

According to the Living Places website, Slater purchased the land from a Native American for a two-year-old heifer and a flint-lock rifle.

In August 1875 construction began of the 3 ft (914 mm) narrow gauge Waynesburg and Washington Railroad, conceived by John Day in 1874 and chartered in 1875.

[4] Its passenger service ended in 1929, and conversion to 4 ft 8+1⁄2 in (1,435 mm) standard gauge followed in 1944 as a wartime measure.

Regular freight service ended on this line in 1976, though part of it still serves (irregularly) for railroad access to a coal mine.

[6] Its southern boundary follows the South Fork of Tenmile Creek, an east-flowing tributary of the Monongahela River.

According to the United States Census Bureau, Waynesburg has a total area of 0.80 square miles (2.07 km2), all land.

The SCI-Greene prison, operated by the Pennsylvania Department of Corrections, is located in Franklin Township, near Waynesburg.

It was bequeathed by Mrs Bowlby, a prominent local citizen who died in 1957, to serve as a children's library.