Prior to the opening of the Cape Cod Canal in 1916, Buzzards Bay Station was located on what was then the north bank of the Monument River at a junction of the main railroad line between Middleborough and Cape Cod and the branch to Wood's Hole. The Wood's Hole Branch crossed the river slightly west of what is now the Cape Cod Canal Railroad Bridge, while the Cape Cod main line continued along the north side of the river before crossing where the river narrowed at Bourne Station. The Monument River was converted into the Cape Cod Canal, which opened in 1916. The Cape Cod Main Line and junction were moved to the south side of the canal, which was later widened in the 1930s.
Originally located near the tracks, the station building is now set back from the train line because of the removal of excess trackage. The station also houses year-round offices and a seasonal visitor's center for the Cape Cod Canal Region Chamber of Commerce.