The Chesapeake and Ohio Railway was a Class I railroad formed in 1869 in Virginia from several smaller Virginia railroads begun in the 19th century. Led by industrialist Collis P. Huntington, it reached from Virginia's capital city of Richmond to the Ohio River by 1873, where the railroad town of Huntington, West Virginia, was named for him.

Collis Potter Huntington was an American industrialist and railway magnate. He was one of the Big Four of western railroading who invested in Theodore Judah's idea to build the Central Pacific Railroad as part of the first U.S. transcontinental railroad. Huntington helped lead and develop other major interstate lines, such as the Southern Pacific Railroad and the Chesapeake & Ohio Railway (C&O), which he was recruited to help complete. The C&O, completed in 1873, fulfilled a long-held dream of Virginians of a rail link from the James River at Richmond to the Ohio River Valley. The new railroad facilities adjacent to the river there resulted in expansion of the former small town of Guyandotte, West Virginia into part of a new city which was named Huntington in his honor.