The section of the Mid-Cape Highway between exit 78 and the Orleans rotary is known to locals as "Suicide Alley" due to the number of fatal accidents that happen on this stretch of two-lane divided freeway with only a berm separating the lanes of traffic.

US 6 is a four-lane road for approximately its first 54 miles (87 km) from the Rhode Island line (crossing into Massachusetts from East Providence, Rhode Island, to Seekonk) to the Cape Cod Canal, except for sections in New Bedford, where it runs along a one-way pair, and Fall River, where it is a two-lane avenue.

The road passes over I-195 (without an interchange) one last time before turning eastward along Martine Street onto the "Narrows", the thin strip of land between the Watuppa Ponds that also carries the interstate between Fall River and Westport.

US 6 is the primary highway serving the towns of Cape Cod, linking the communities to the Sagamore Bridge and to subsequent points north and west.

The bridges from the Cape Cod Canal to Oak Street in Barnstable (a half-mile [0.80 km] west of exit 68), are unusual in their construction since they are made out of concrete and granite.

At exit 78, the Mid-Cape Highway becomes a two-lane divided 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 from 1989–1992.

In Provincetown, the road is locally maintained, and ends as a divided highway before meeting Route 6A at the Cape Cod National Seashore.

The only remnants of the old path is the odd turn Old Bedford Road takes before intersecting, having once been a separate street; the original alignment would have extended straight to US 6.

In 2011, the Veterans Memorial Bridge opened, relocating US 6/Route 138 to a brief higher-speed freeway-like roadway over a taller drawbridge between Somerset and Fall River.

The connection between US 6 west of the construction site and its now-closed alignment to the closed and unused Brightman Street Bridge was closed at this time, with the former alignment being renamed from Grand Army of the Republic Highway (GAR Highway), which is another name for US 6 nationwide, to Slade's Ferry Boulevard.

The interchanges and intersections at the eastern end of each bridge have been reconstructed multiple times; when Route 79 construction is finished, both the brief US 6/Route 138 bridge expressway and Route 79 expressway will end here, with US 6/Route 79/Route 138 traveling along the Davol Street one-way pair to the south (US 6 will continue to exit Davol Street at President Avenue, as it has since the construction of the now-closed central section of the Western Fall River Expressway (MA 79) and the Davol Street one-way pair in the early-to-mid-1970s.

After the Provincetown US 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.

The exit tabs and gore signs for the new signage would be designed however so the milepost numbers could fit on them, if changed, sometime in the future.

[4] The winning bid for the scaled down contract simply to replace the signs was made by Liddell Bros. Inc. of Halifax and announced on February 7, 2017.

[6][7] MassDOT plans to convert one of the dual carriageways on the little-used eastern end of US 6 in Provincetown to a car-free bike path, scheduled for construction from 2024 to 2026.