The region is underlaid with a stratum of coking coal. The area is also rich with methane, which is currently being drilled as an alternative fuel source. At one time, there were also natural gas and oil deposits in the area. 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.
As of the census of 2000, there were 4,184 people, 1,619 households, and 869 families residing in the borough. The population density was 5,038.6 people per square mile (1,946.3/km²). There were 1,811 housing units at an average density of 2,180.9/sq mi (842.4/km²). The racial makeup of the borough was 96.94% White, 1.63% African American, 0.10% Native American, 0.57% Asian, 0.05% Pacific Islander, 0.17% from other races, and 0.55% from two or more races. Hispanic or Latino of any race were 0.65% of the population.
There were 1,619 households out of which 24.1% had children under the age of 18 living with them, 38.4% were married couples living together, 11.6% had a female householder with no husband present, and 46.3% were non-families. 38.2% of all households were made up of individuals and 16.7% had someone living alone who was 65 years of age or older. The average household size was 2.24 and the average family size was 2.99.
In the borough the population was spread out with 18.6% under the age of 18, 24.2% from 18 to 24, 24.8% from 25 to 44, 17.8% from 45 to 64, and 14.5% who were 65 years of age or older. The median age was 30 years. For every 100 females there were 97.5 males. For every 100 females age 18 and over, there were 97.4 males.
The median income for a household in the borough was $30,990, and the median income for a family was $42,933. Males had a median income of $31,577 versus $22,458 for females. The per capita income for the borough was $15,333. About 8.0% of families and 13.0% of the population were below the poverty line, including 10.5% of those under age 18 and 11.7% of those age 65 or over.