The Pittsburgh, Fort Wayne and Chicago Railway was a major part of the Pennsylvania Railroad system, extending the PRR west from Pittsburgh, Pennsylvania, via Fort Wayne, Indiana, to Chicago, Illinois. It included the current Norfolk Southern-owned Fort Wayne Line east of Crestline, Ohio, to Pittsburgh, and the Fort Wayne Secondary, owned by CSX, from Crestline west to Tolleston in Gary, Indiana. CSX leased its entire portion in 2004 to the Chicago, Fort Wayne and Eastern Railroad (CFE). The remaining portion of the line from Tolleston into Chicago is now part of the Norfolk Southern's Chicago District, with a small portion of the original PFW&C trackage abandoned in favor of the parallel lines of former competitors which are now part of the modern NS system.

The Pennsylvania Railroad, legal name The Pennsylvania Railroad Company, also known as the "Pennsy", was an American Class I railroad that was established in 1846 and headquartered in Philadelphia. It was named for the commonwealth in which it was established. At its peak in 1882, the Pennsylvania Railroad was the largest railroad, the largest transportation enterprise, and the largest corporation in the world.