In the South Hills, PA 51 (Saw Mill Run Boulevard), along with US 19, is one of the major routes in and out of Pittsburgh, as it provides access to several bridges and tunnels.

In North Union Township, PA 51 divides for 0.7 miles (1.1 km); the road has a large median that is home to several businesses.

About 2,000 feet (610 m) northwest of PA 981, it also intersects Interstate 70 at exits 46 A-B to form a full cloverleaf interchange.

[3] Upon entering Allegheny County, PA 51 is called Hayden Boulevard, and it meets with Pennsylvania Route 136 at a diamond interchange.

In West Elizabeth, after crossing the Monongahela River via the Regis R. Malady Bridge, PA 51 immediately intersects with Pennsylvania Route 837.

It then continues towards Jefferson Hills in the northwest, where it meets the northern terminus of Pennsylvania Route 43 (Mon-Fayette Expressway) at exit 54.

[5] At the southern tip of Pittsburgh, PA 51 intersects the northern terminus of Pennsylvania Route 88 before continuing towards the north as Saw Mill Run Blvd.

North of Coraopolis, PA 51 continues to parallel the Ohio River as University Boulevard in Moon Township.

It then becomes Stoops Ferry Road and passes through Crescent Township on McGovern Boulevard before entering Beaver County.

In South Beaver Township, PA 51 intersects Pennsylvania Route 168 and continues towards the northwest as Constitution Boulevard.

The Saw Mill Run Boulevard section of the highway was the first direct connection between Pittsburgh and the South Hills once the Liberty Tunnel was completed.

In 1964, while designated as "the worst bottleneck in Western Pennsylvania," a plan was made to turn the crowded highway into an expressway.

The plan was proposed to the Department of Highways and included a renovation of the Liberty Tunnel, several widening projects, new turning lanes, and a central median.

Interest in the expressway declined once the Southwestern Pennsylvania Regional Planning Commission expressed concerns about business along the corridor, and the project was dropped in 1973.

A cloverleaf has been established to direct traffic between Elizabeth's main street (known as Center Ave and McKeesport Road on different ends of town), but its narrow and winding design makes it difficult for trucks to access Route 51 southbound.

As a result, they were directed to enter onto Route 51 northbound, cross the bridge over the Monongahela River, and use a special u-turn exit to reach southbound lanes of travel.

This truck route was removed after a weight limit was imposed on the Regis R. Malady Bridge over the Monongahela River.