Route 3 is a southward continuation of U.S. Route 3, connecting Cambridge, Massachusetts with Cape Cod. All of it, except for the northernmost end in downtown Boston and Cambridge, is a freeway.

The section from Boston to Braintree is also marked as Interstate 93 and U.S. Route 1 and is known in downtown Boston as the Central Artery, and south of downtown as the Southeast Expressway. In Braintree, I-93 and US 1 split to follow the Yankee Division Highway to Interstate 95, and Route 3 continues south on its own, as the Pilgrims Highway. This section extends to a junction with U.S. Route 6 in Sagamore, just before the Sagamore Bridge over the Cape Cod Canal where Route 3 originally ended at rotary. Replacement of this rotary with an elevated "flyover" interchange was completed in November 2006.

Because Route 3 and U.S Route 3 are treated as the same route by the Massachusetts Department of Transportation (MassDOT), mileposts increase continuously from Bourne to the New Hampshire border.

Route 3 can be said to have three segments; the Pilgrims Highway, its concurrency with Interstate 93, and its route after leaving I-93 in Boston and Cambridge.

Pilgrims Highway is the part of Route 3 that stretches from the intersection with US 6 in Bourne to the junction with Interstate 93 in Braintree.

Route 3 runs concurrently with Interstate 93 and U.S. Route 1 from Exit 7 in Braintree to Exit 26 in Boston. See Interstate 93.

Route 3 exits I-93 at Exit 26, passes through Leverett Circle, and runs for a short way along the Charles River to the Longfellow Bridge where it crosses over to Cambridge and joins Memorial Drive. It is on Memorial Drive that the designation changes to US-3 which continues northward toward New Hampshire.

Route 3 began as a new designation for New England Highway 6 in 1927 when the U.S. Highway system was created and New England highway Route 3 was chosen to be US 6. The former NE 6 then took the route 3 number with U.S. Route 3 designated north of its intersection with U.S. Route 1 and Massachusetts Route 3 to the south. The route was basically a connected system of two-lane roadways up until the 1950s with the exception of Route 3's original path through Boston which paired it with US 1 on Park Drive, the Riverway and the Jamaicaway and then along its own path in Mattapan and Dorchester along the Arborway, Morton Street and Gallivan Boulevard.

Before the road was rerouted, the road continued over the Cape Cod Canal via the Sagamore Bridge to the Bourne Rotary, to the south of the Bourne Bridge. This arrangement changed after 1951.

The Plimoth Plantation Highway, a two-lane expressway that connects Route 3 with Route 3A, was once signed as Route 3 before the southernmost portion of the freeway to Cape Cod was finished.

The first section of the Pilgrims Highway was built as a bypass of Plymouth in the early 1950s. The mid-1950s saw an extension of this bypass route south to the Sagamore Bridge and north to Kingston. The northern section of the highway was built next with a connection from Derby Street in Hingham to the Southeast Expressway opening in 1959. (Portions of this road run alongside the Old Colony Railroad's mainline, now used by the MBTA Old Colony Lines Commuter Rail, and the MBTA Red Line rapid transit.) Finally the last sections between Hingham and Duxbury were completed by 1963 when the Route 3 designation was moved onto the completed freeway. The former Route 3 highways became Route 3A in Quincy and from Kingston south, the remainder became Route 53. Route 3 was connected to the Southeast Expressway in Milton by using Granite Avenue as a link from Gallivan Boulevard. Until around 1965, the northern portion of the Pilgrims Highway, from current Exit 15 (Derby Street) in Hingham, was also signed as Route 128, which continued past the exit on surface streets to Hull. However, by 1966 the 128 designation was removed past its intersection with Route 3 in Braintree (and thus from the Pilgrims Highway entirely) and the surface portion became Massachusetts Route 228. Route 3 was then taken off its remaining pathway along surface streets in Boston and extended up the Southeast Expressway and Central Artery in 1971 to the Storrow Drive exit. The routing of Route 3 has changed little since that time.

A re-signing project from 2006 to 2009 changed exit 20 to exit 20A for I-93 south and exit 20B for I-93 north. In the process, the ramp carrying Route 3 to I-93 north was no longer signed as part of Route 3. Separate signs indicating Route 3's routing along I-93 were installed on exit sign support poles in 2011.

The MassDOT is currently looking in to the possibility, in a similar manner to what has been ongoing for a 14+ mile length of Route 128's southwest section, of widening Route 3 from I-93 to the Sagamore Bridge from four to six lanes with new bridges and new on- and off-ramps, and will include upgraded interchanges with new acceleration and deceleration lanes. The project is expected to cost $256 million.

Route 3 was one of the freeways whose exits were once numbered with the "25 is 128" system, in which the Braintree Split was numbered "Exit 25" (due to it being the exit for Route 128), with numbers increasing away from Boston and decreasing toward Boston. Under the old system, the Sagamore Rotary was (on paper) "Exit 43". When the first 22 miles (35 km) of the highway were resurfaced in 1975-76, the new numbers were instituted in that section. When the Braintree section was resurfaced in 1978, the rest of the new numbers were posted, leaving a two-year gap when half the highway was on the new system while the other half was on the old system. During that time, the exit to Route 14 was "Exit 11" northbound and "Exit 33" southbound.