The Chesapeake & Ohio (C&O) Railway helped open southern West Virginia's coalfields by allowing operators to get to the coal and to get the coal to market. It led to the growth of towns like Huntington, Hinton, and Thurmond. Many West Virginians have worked for the C&O or its later versions.

The C&O was formed in 1868 by merging two railroads. It was backed by Collis P. Huntington, who helped complete the first transcontinental railroad. He expanded the C&O west from Virginia and east from a new town called Huntington on the Ohio River. Building through the mountains was hard, dangerous, and expensive, but the railroad was finished in 1873.

After struggling with money problems, the C&O recovered and grew, reaching cities like Cincinnati, Columbus, and even Chicago. It built many branches in West Virginia to reach coal and timber areas. The C&O kept expanding and survived the Great Depression better than most railroads thanks to coal.

In 1962, the C&O bought the B&O. A decade later, it merged into the Chessie System, which became part of CSX in 1980. Today, CSX and Norfolk Southern are the two main railroads in West Virginia.