The Baltimore and Ohio Railroad (B&O) was one of the oldest railroads in the United States and the first common carrier railroad, with an original line from the port of Baltimore, Maryland, west to the Ohio River at Wheeling and a few years later also to Parkersburg, West Virginia. It is now part of the CSX network, and includes the oldest operational railroad bridge in the world. The B&O also included the Leiper Railroad, the first permanent railroad in the U.S. In later years, B&O advertising carried the motto: "Linking 13 Great States with the Nation." Part of the B&O Railroad's immortality has come from being one of the four featured railroads on the U.S. version of the board game Monopoly, but it is the only railroad on the board which did not serve Atlantic City, New Jersey, directly.

When CSX Corp. established the B&O Railroad Museum as a separate entity from the corporation, some of the former B&O shops in Baltimore, including the Mt. Clare roundhouse, were donated to the Museum while the rest of the property was sold. The B&O warehouse at the Camden Yards rail junction in Baltimore now dominates the view over the right-field wall at the Baltimore Orioles' current home, Oriole Park at Camden Yards.