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 Automobile While Fayette County is a generally rural area and is not directly tied into the interstate system, it features four-lane access to the city of Pittsburgh and several of its major suburban areas. Future state highway plans call for the establishment of direct freeway connections with Pittsburgh to the north and Morgantown, West Virginia to the south. U.S. and Pennsylvania Highways - Pennsylvania Route 21- designated as the Roy E. Furman Highway, it serves as one of the main routes through Greene County, then this route travels crosses the Monongahela River in Masontown and terminates in Uniontown
- U.S. Route 40- a portion of the famous National Road, it connects in the west with Washington County and provides access to the Pittsbugh edge suburb of Washington; after forming part of a freeway bypass of Uniontown, it becomes a major two lane mountain highway heading toward Maryland
Business U.S. Route 40 (Brownsville)- recent designation for a 1.5-mile (2.4 km) two-lane section of the original path of US 40 that has been replaced by a realigned route; highway runs in its entirety through Redstone Township and was kept as part of the federal highway system to prevent a decrease in traffic for area businesses
Business U.S. Route 40 (Uniontown)- bypassed by a freeway through the more suburbanized areas of the small city, the original routing of US 40 has been turned into this downtown connector; from its western expressway terminus, the route runs as a narrow four-lane street toward the business district, at which its eastbound and westbound lanes split to become East Fayette St and East Main St respectively; the road then continues with a two-lane segment through hilly but populated South Union Township, before ending as US 40's freeway stretch transitions to a mountain climb- Pennsylvania Route 43- part of the Mon-Fayette Expressway, it serves as a toll freeway currently connecting Uniontown to the southern Pittsburgh suburb of Jefferson Hills, with eventually plans to extend the route to the city limits; to the south, it currently connects with Springhill Township, and eventually will also provide freeway access to Morgantown, West Virginia
- Pennsylvania Route 51- provides the major connection between Uniontown and Pittsburgh city limits, which functions as a four-lane route except during its final mile as a major Uniontown city street
- Pennsylvania Route 88- winding riverfront highway that connected Pittsburgh's southern suburbs and the Monongahela Valley, before briefly entering Fayette County to terminate in Port Marion
- U.S. Route 119- provides access to Morgantown in the south as a rolling two-lane highway, before becoming Fayette County's main street; serves as part of a freeway bypass of Uniontown, then functions as a four lane route through Connellsville, before traveling toward the Pittsburgh edge suburb of Greensburg
- Pennsylvania Route 166- rural connecting route between Point Marion and a portion of Brownsville Township just outside of Brownsville, this highway connects small communities in the eastern portion of the county
- Pennsylvania Route 201- its trajectory shaped in almost the figure of an arch, this route provides access between Connellsville and southwestern Westmoreland County, and serves as a major cross-county truck route
- Pennsylvania Route 281- rural connecting route between Maryland border and Somerset County, this highway also serves tiny Markleysburg and Henry Clay Township
- Pennsylvania Route 381- a rural mountain highway between the West Virginia border and Westmoreland County, the route runs through the hart of Fayette County's Laurel Highlands region; through the area surrounding Ohiopyle State Park, it is a designated as a scenic route
- Pennsylvania Route 653- mountain cut-off highway connecting Springfield Township with Somerset County; the portion of the route through Laurel Ridge State Park is designated as a scenic highway
- Pennsylvania Route 711- mountain highway terminating in Connellsville and connecting with Westmoreland County, this route is the backbone of the Laurel Highlands
Truck Pennsylvania Route 711- bypass of Downtown Connellsville that is partially cosigned with US 119 near its southern terminus and follows somewhat narrow but relatively flat city streets to avoid the hilly city center- Pennsylvania Route 819- rural access route from Vanderbilt to the small Westmoreland County city of Mount Pleasant
- Pennsylvania Route 857- rural highway running from a freeway exit in South Union Township to the West Virginia border that is largely bipassed by Route 43
- Pennsylvania Route 906- short, riverfront highway that terminates in Washington Township, just outside the Fayette City line; runs through Belle Vernon and then serves as the main access route to the Westmoreland County town of Monessen
- Pennsylvania Route 982- two lane access route connecting Bullskin Township with the city of Latrobe in Westmoreland County
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