In 1783, Fayette County was created out of the southern part of Westmoreland County and named after the French hero of the American Revolution, the Marquis de LaFayette. It was also the location of the Whiskey Rebellion (1791-1794), when frontier farmers protested a federal excise tax on whiskey with attacks on the tax collector. Though the insurrection ended in surrender, it provided the first real test of the new U.S. Constitution.

In the late 18th century, industry began to appear in the area with furnaces locating in the mountains to be near the iron ore. Because of its strategic location on the Monongahela River, the county quickly became a center for the construction and dispatch of flatboats, keelboats, and later, steamboats.

This past prosperity has faded and Fayette County has experienced severe economic distress, largely due to the decline of coal mining and other heavy industry. The result has been more than 30 years of poverty for many residents in the foothills of the Allegheny Mountains. Since the 1950s, the local workforce has been struggling to make the transition from a manufacturing to a service economy.

A majority of residents remain unemployed, underemployed, or employed at less than living wages. The median household income for Fayette County residents is $8,000 below the state's. More than 19 percent of Fayette County residents live in poverty, the second highest rate in the state and the highest among rural Pennsylvania counties.