The southern entrance of US 119 is at the West Virginia state line one-half-mile south of Point Marion.

US 119 is in the National Highway System from the West Virginia state line to Exit 0 of PA Turnpike 66, and from US 22 to US 219.

US 119 merges with US 40 to form part of the George C. Marshall Parkway, which bypasses the city of Uniontown to the west and north.

Shortly after the Connellsville Road exit, US 119 passes Penn State Fayette, The Eberly Campus.

The highway leaves Connellsville as Memorial Boulevard and heads to the north intersecting with the southern terminus of PA 982 (Pleasant Valley Road).

Shortly after leaving Youngwood, US 119 intersects the Lincoln Highway (US 30), which bypasses Greensburg to the west and south.

At PA 130, Pittsburgh St., US 119 turns to the right and leaves Greensburg as Harvey Ave and heads to the northeast toward the historical Hannastown.

Once leaving Greensburg US 119 becomes predominantly a two-lane road again for the first time since joining the Uniontown bypass nearly 40 miles (64 km) south.

Immediately after passing Indiana, the Buffalo-Pittsburgh Highway becomes a two-lane road again north of an interchange with PA 110 and continues to Home.

US 119 is concurrent with PA 36 for four blocks before making a left turn on Hampton Ave. Route 119 leaves Punxsutawney shortly thereafter as Ridge Ave. and heads east toward Big Run.

After passing through Big Run as Main St., the Buffalo-Pittsburgh Highway turns to the north-northeast toward Sykesville, PA.

Originally, instead of ending at US 219 in Sandy Township, it followed US 219's current alignment for 44 miles (71 km) north to Wilcox.

In 1993, an expressway from the southern end of the Uniontown bypass to Big Six Road in Georges Township was built parallel to US 119.

In 2009, the Pennsylvania Department of Transportation (PennDOT), Pennsylvania Turnpike Commission (PTC), and West Virginia Division of Highways (WVDOH) had planned on submitting an application to the American Association of State Highway and Transportation Officials (AASHTO) on realigning US 119 onto the Mon–Fayette Expressway south of Uniontown all the way to the Mon–Fayette's southern terminus with Interstate 68 near Cheat Lake, West Virginia east of Morgantown, where it would briefly run concurrent with I-68 once the West Virginia section of the Mon–Fayette Expressway opened in 2011.