The ultimate goal of the highway is to provide a high speed north–south connection between Morgantown and the eastern side of Pittsburgh while revitalizing economically distressed Monongahela River Valley towns in Fayette and Washington counties, serving as an alternative to Interstate 79 to the west, as well as relieving the PA 51 alignment from Pittsburgh to Uniontown.

The Mon–Fayette Expressway begins at a diamond interchange with I-68 in Cheat Lake in Monongalia County, West Virginia, heading north as a four-lane freeway signed as WV 43.

The route passes to the west of an industrial park before reaching an interchange with Big Six Road which provides access to US 119 and PA 857.

Following this, the toll road heads northwest through rural areas to the south of Brownsville, crossing the Dunlap Creek into Luzerne Township.

PA Turnpike 43 heads into Carroll Township and makes a sharp curve to the west, continuing through more rural areas.

The Mon–Fayette Expressway crosses the Mingo Creek Viaduct into Union Township and continues north through wooded areas with some fields and mines.

The Mon–Fayette Expressway continues a short distance to its current northern terminus, where the traffic lanes turn west as Jefferson Boulevard and head to PA 51.

Unlike the Pennsylvania Turnpike mainline and the Northeast Extension, which uses long-distance tickets, the Mon–Fayette Expressway collects fixed tolls at regular intervals.

Despite severe financial constraints, PennDOT built the remainder of the ramps at the U.S. 40 cloverleaf along with a separate 2-mile (3.2 km) stretch of highway near California in the early 1980s.

Rather than cancel the project, local leaders touted it as a means of stimulating the distressed economy; providing a link from the City of Pittsburgh to West Virginia along which manufacturing facilities and other industry could be located.

The project was redesignated as the Mon–Fayette Expressway, a portmanteau of Monongahela River Valley and Fayette County, two of the areas the new road would connect.

While PennDOT assessed preliminary engineering and right-of-way options in the 1970s and early 1980s, the PTC accelerated design work and began unveiling detailed plans in earnest by the late 1980s.

Funding appropriated through the PTC allowed construction to resume in 1988, and on October 12, 1990, the entire stretch from U.S. Route 40 to Interstate 70 opened to traffic.

Aside from being part of a larger project, the new segment was designed to provide high speed access between the Uniontown bypass, Fairchance, and a new business park.

[14][15] In the early 1990s, the Pennsylvania General Assembly dedicated a portion of state fuel excise tax revenue to the PTC.

[15] The Joe Montana Bridge, named after the Pro Football Hall of Fame quarterback who grew up in the immediate area in nearby Monongahela, Pennsylvania,[16] is located along the route.

In 2006, construction began on a 17-mile (27 km) stretch connecting the oldest section of the expressway near Fredericktown to the northern terminus of the Chadville Demonstration Project.

The first phase involved construction of an 8-mile (13 km) section of expressway running parallel to a hazardous stretch of U.S. Route 40 between Brownsville and Uniontown.

The final contracts to build the Cheat Lake and Interstate 68 interchanges were respectively awarded in December 2008 and July 2009, partly as a result of an ARRA fund infusion.

Noteworthy features on the West Virginia section include two high-level bridges, along with the I-68 interchange, which is a hybrid design that utilizes both high-speed ramps and at-grade intersections.

[19] If the second phase is built, the I-68 interchange will be upgraded to a directional T.[citation needed] The remaining 13.7 miles (22.0 km) of highway in Allegheny County between PA 51 and I-376 has yet to be constructed.

After a review of several alternative alignments designated by colors (green, yellow, orange, and blue), a series of public meetings hosted by the Pennsylvania Turnpike Commission sought feedback from residents likely affected by the expressway's construction.

Kennywood acquired nearly 50 acres (20 ha) of property for a potential expansion of the park on the condition that the leg to Monroeville is built.

[27] The second leg of the Southern Beltway, which will proceed in construction as had already been announced, will be the first portion of the two highways that will be built with the new funding available,[25] with a planned opening to I-79 in 2019.

[29] In December 2014, it was reported that the Mon–Fayette Expressway and the Southern Beltway might get additional funding through foreign investors who obtain an EB-5 visa in exchange for investing at least $500,000 for public projects.

[30] On June 18, 2015, the PTC announced that the segment for the Mon–Fayette Expressway from Jefferson Hills to Monroeville will receive some Act 89 funding and will return to the design phase.

Construction on the section of the expressway between PA 837 in Duquesne and I-376 in Monroeville is expected to follow, but may be delayed due to funding shortfalls resulting from the COVID-19 pandemic.

[citation needed] In March 2021, a PTC engineer said that preliminary work on the Mon–Fayette Expressway from Jefferson Hills to PA 837 would begin after the projected completion of the Southern Beltway later that year.

[34] In June 2021, PTC officials told Pennsylvania state legislators that construction on the section to Duquesne could begin as early as 2022.

[22][23] In order to provide access to certain interchanges within the Uniontown-to-Brownsville project, the PTC had to build several toll-free connectors, the most notable of which extended a four-lane section of U.S. Route 40 near Brownsville, eliminating a forty-year-old freeway stub in the process.