[1][2] The first state highway in Massachusetts was a 5305.17-foot (1617.02 m) section of Fitchburg Road (now Main Street, part of Route 119) in Ashby.

The road was paved with 15–20 foot (4.5–6 m) macadam, with work beginning August 21, 1894 and ending July 15, 1895.

[3][4] Massachusetts first gained numbered routes in 1922, with the formation of the New England Interstate Highways.

The establishment of the U.S. Highway System in 1926 resulted in several of the New England Interstate routes having to be renumbered.

The Massachusetts Department of Conservation and Recreation's Bureau of Engineering still manages and/or operates a number of parkways across the Commonwealth.

Additionally, there are seven other towns which have Interstates or US Routes, but do not have any Massachusetts state highways: Chester, Holland, Mattapoisett, Montgomery, New Ashford, Shutesbury and Wilbraham.

A number of signs installed on the U.S. Route 3 expressway are of a cut-out design, without the black background.

The Lowell Connector was technically the only "auxiliary" route in the state, having been formerly signed as Interstate 495 Business Spur in the 1960s.

Massachusetts converted from sequential to mileage-marker exit numbering on its freeways in 2021 with the exception of I-291, I-391, Lowell Connector, and Route 213.

[5] This change was supposed to be made starting in 2016 when a project to renumber all sequential numbered exits to those based on highway mileposts.

[8] Prior to renumbering, five freeways in Massachusetts contained irregular exit numbering patterns: