Among the proponents of the Cape Cod Branch Railroad were Col. Richard Borden of Fall River, who saw the new line as an opportunity to bring more traffic and business through his hometown.

He was at one time president of the Bay State Steamboat Company, which together with the Old Colony Railroad formed the noted "Fall River Line".

[2] In the spring of 1854, construction continued, with the railroad reaching Barnstable village May 8, Yarmouth Port May 19, and finally Hyannis on July 8, 1854.

In 1986, Amtrak began operating the Cape Codder during summer weekends from New York City to Hyannis, until it was terminated in 1996.

Bay Colony was also the sole operator of freight rail on the Cape from 1987 to 2007, until their contract expired and service was taken over by Massachusetts Coastal Railroad.

The Cape Cod Central Railroad continues to operate seasonal tourist excursions, departing from Hyannis and Buzzards Bay and occasionally including stops at West Barnstable and Sandwich.

As of 2020, the MBTA is conducting a study to evaluate the feasibility of implementing such service in conjunction with the currently-underway South Coast Rail project.

Other regular operations include interchanging with CSX in Middleborough and transporting material for the ongoing South Coast Rail project.

Mass Coastal has been in conflict with proponents of a new rail trail that wish to replace the line between Bourne and Camp Edwards with a new branch of the Shining Sea Bikeway.