From Harrisburg/Enola, the railroad travels northwest following the path of the Susquehanna River parallel to U.S. Route 11/15, passing through the communities of Marysville, Cove, and Duncannon.

Once at Altoona, the railroad arrives at the base of the Allegheny Mountain Front, which it must climb to reach Johnstown and Pittsburgh.

Originally constructed by the PRR in 1850, this large complex of shops is what gave the city of Altoona its worth and structure.

Leaving Altoona, the railroad travels at a 1.76% grade up the east slope of the Alleghenies, negotiating the famous Horseshoe Curve during that climb.

Originally constructed by the PRR in 1854, the 220-degree curve was the solution for the railroad to gain enough elevation around a valley to reach the higher land across to continue west.

Constructed mainly by immigrants, the curve was built by cutting into the hillside around Kittanning Point and filling in the necessary places for the railroad right-of-way to be laid.

Today, the curve functions as a tourist attraction for both railroad enthusiasts and the rest of the public, and is a magnet for drawing visitors from all over the globe.

East of Gallitzin, the railroad passes through Bennington Curve, the site of a PRR passenger wreck in 1947 killing 16 people and injuring over 100.

Past Bennington Curve at a railroad timetable station called "SF", the three tracks split.

[4] Past Gallitzin, the railroad passes through the small town of Cresson, where all of the Pittsburgh Line's tracks come back together.

Past Cresson, the railroad passes down the Alleghenies' west slope, through the towns of Lilly, Cassandra, Portage, Wilmore, Summerhill, South Fork, Mineral Point, Parkhill, and East Conemaugh before reaching Johnstown at the bottom of the mountain.

Helper locomotives are used by Norfolk Southern to assist heavy trains over mountainous portions of the Pittsburgh Line.