Route 6 is the portion of the cross-country U.S. Route 6 highway in the state of Massachusetts. Route 6 runs 117.46 miles (189.03 km) in the state connecting Providence, Rhode Island to Fall River, New Bedford, and Cape Cod. In the Fall River and New Bedford areas, Route 6 is a secondary highway paralleling Interstate 195. Within Cape Cod, Route 6 is the primary highway interconnecting the towns of the area.

Route 6 is a 4-lane arterial road for approximately its first 54 miles (87 km) from the Rhode Island line (crossing into Massachusetts from East Providence to Seekonk) to the Cape Cod Canal, except for sections in New Bedford (where it runs along Mill and Kempton Streets, two one-way city streets) and Fall River (where it runs along a two-lane President Avenue).

After crossing the canal via the Sagamore Bridge, it becomes a freeway, known as the Mid-Cape Highway. From Bourne to Dennis at the Exit 9A/B cloverleaf, the freeway is 4 lanes. The bridges from the Cape Cod Canal, to Oak Street in Barnstable Village (a half-mile west of Route 132), are unique in their construction since they are made out of concrete and granite. The road then reduces to a two-lane freeway with plastic stanchions posted on a small asphalt median. The two-lane freeway section has a secondary, less-formal name of "Suicide Alley", due to the high number of fatalities from head-on collisions before the median improvements were constructed. (When the two-lane freeway stretch was first built, it was marked with passing zones like any other two-lane highway. The small asphalt/stanchion median was built in stages beginning in 1989 and finishing in 1992.) The Mid-Cape Highway carries a speed limit of 55 on the standard freeway and 50 on the two-lane freeway. It remains like this until Orleans, where the freeway ends at a large rotary (Mile 90.6).

Through Eastham and North Truro, U.S. 6 is a 4-lane surface street. Through Wellfleet and southern Truro, U.S. 6 is a former 3-lane road converted to 2 lanes with shoulders. In Provincetown, U.S. 6 ends as it started in the state, as a surface expressway once again until it comes to an end at Route 6A at the Cape Cod National Seashore. For the last several miles of its existence near Provincetown Route 6 east is actually heading west-southwest.

Before the U.S. Highway system, the route from Rhode Island to Bourne, and from Orleans to Provincetown, was part of New England Interstate Route 3 (NE-3). Within the Upper Cape, however, NE-3 went along what is now Route 28 between Bourne and Orleans. The U.S. 6 designation was instead applied to the route on the north shore of Cape Cod, which was known as New England Interstate Route 6 before 1926 (now Route 6A).

When U.S. 6 was first routed through Provincetown in 1926, the highway was signed along the rather narrow Commercial Street. After the Provincetown U.S. 6 bypass was built, congestion and the increasing size of automobiles forced the town to post most of Commercial Street (all but the easternmost mile that hits the Truro line) as one-way westbound. Route 6A, when signed, was placed along the paralleling Bradford Street instead. There was an alternate plan at the time to make Bradford one-way westbound and Commercial one-way eastbound (which would have made both roads Route 6A), but this was rejected, as the town decided instead to let incoming traffic through the heavy Commercial Street (almost entirely pedestrian) business district.

U.S. 6 was briefly signed on current I-195 between Route 105 and Route 28; however, when I-195 was completed, and the I-195 designation took over that section of freeway, U.S. 6 reverted to its older route.

Formerly, U.S. 6 took both sides along the Cape Cod Canal (and was signed as "BYPASS 6"), but is now routed only on the north side (The south side is now signed "TO 6" from the Sagamore Bridge to the Bourne Bridge). However, a single "BYPASS 6" sign still exists along Sandwich Road just north of the Bourne Bridge rotary.

The westbound exit numbers in Sagamore are out of order: First is Exit 1C, then Exit 1A, then Exit 1B. On the eastbound side, Exits 1A-B are combined into one exit, with three exit only lanes and US-6 shrinking down to one lane. US-6 shrinks to one lane westbound too, after Exit 1B, before gaining three lanes again.

The Orleans Rotary was once officially Exit 13. A sign labeling the turnoff to Routes 6A/28 once marked it as "Exit 13S", however the signage was removed in 1985.

Westbound entering New Bedford

Southbound entering Eastham

Westbound start at Provincetown. This sign was erected in August or September 2010.