The Middleboro Line opened in 1846 as part of the Fall River Railroad, which was merged with the Old Colony in 1854. For decades this was the main route for Boston-Fall River service, but after the New Haven took over that service was increasingly routed via the Boston & Providence main line. The Middleboro Line also was used by Boston-Cape Cod trains. The New Haven discontinued passenger service on this line (as well as the other Old Colony lines) in 1959.

The MBTA restored passenger service to Middleboro in 1997. There has been some interest in extending service down to Cape Cod, most recently by Cape Rail Inc., which has proposed running passenger trains from Hyannis to Middleboro. So far, though, no serious action has been undertaken to make this a reality.