CSX is the successor corporation to the Chessie System, created as a result of the merger of other railroads with the Chessie System in 1980.

In the 1970s, it was evident the Norfolk & Western (N&W) and the Southern Railway System were progressing toward a merger. To remain competitive the Chessie System sought a partner for itself. The other railroad system in the South most affected by the pending N&W-Southern merger was the Family Lines, a loose affiliation of the Seaboard Coast Line and the Louisville & Nashville (L&N) railroads and their predecessor lines. On November 1, 1980, the Chessie System and the Family Lines merged into the CSX Corporation. The merger was complex as the two systems retained separate identities for some time, and the L&N did not merge into the Seaboard Coast Line corporation until 1982.

In 1999, CSX and Norfolk Southern absorbed Conrail, the major railroad in the northeast, and divided its lines between themselves. Thus CSX and Norfolk Southern dominated rail transportation in the eastern United States at the beginning of the 21st century. CSX has more than 20,000 miles of track in the eastern United States, nearly 1,200 of which is in West Virginia.