Past the Derby Line–Rock Island Border Crossing, the road continues into Canada as Quebec Autoroute 55.

Before leaving the city limits, a high-occupancy vehicle lane begins that has its own set of interchanges up to exit 38.

At the Windsor–Windsor Locks town line, it meets the eastern terminus of the Route 20 expressway, which provides direct access to Bradley International Airport.

[7] A couple of miles further north, I-91 crosses the Connecticut River on the Dexter Coffin Bridge into East Windsor.

After traveling through East Windsor and Enfield, it crosses the state line, at milepost 58, into Longmeadow, Massachusetts.

[8] I-91 extends 55 miles (89 km) through the Pioneer Valley of western Massachusetts paralleling the Connecticut River.

[15] I-91 serves as the major transportation corridor through three Massachusetts counties, linking the cities of Springfield, Northampton, and Greenfield.

[11] Continuing north, I-91 enters Hatfield, where it begins a straight section—nearly six miles (9.7 km) without a bend in the road.

The major control cities in Vermont are Brattleboro, White River Junction, St. Johnsbury, and Newport.

Brattleboro's main retail strip is located at and just south of the exit 3 trumpet interchange and traffic circle.

White River Junction, listed as a control city on mileage signs as far south as Greenfield, Massachusetts, is where I-91 and I-89 meet and provide access to many points in Vermont and New Hampshire, at exit 10.

It enters Orange County, passing through Thetford, Fairlee, Bradford, Newbury, and Wells River.

It continues into the Caledonia County communities of Ryegate, Barnet and Waterford, before coming to its next major intersection in St. Johnsbury at the northern terminus of I-93, providing access to the White Mountains of New Hampshire and the Greater Boston area.

Here, it reaches the highest point on the road, just north of milemarker 150 on Sheffield Heights, elevation 1,856 feet (566 m).

While paralleling I-91 in Vermont, US 5 is never concurrent with the freeway but remains its own two-lane road, except for a portion in White River Junction where it is a four-lane divided surface arterial.

[37] In Massachusetts from Bernardston to Northampton, I-91 follows an abandoned right-of-way of the New York, New Haven and Hartford Railroad.

To support plans for urban renewal along the "low value" waterfront, the highway crossed the Connecticut River to parallel active New York, New Haven and Hartford Railroad tracks on the Springfield side of the river, bypassing West Springfield and Agawam, Massachusetts.

In 2009, the northbound rest area in Hartford was closed, creating a 90-mile (140 km) gap in on-highway facilities.

At the present time, there exist two intermediate rest areas with facilities in each direction, in addition to a welcome center at each end of the state.

[41] In the early 1990s after the I-284 project was canceled, the exit 44 interchange in East Windsor, Connecticut, was altered as it was designed to be part of the freeway.

[42] In 2005, the Massachusetts Highway Department completed a rebuild of on- and offramps in Springfield to reduce accidents caused by weaving near the tightly spaced exits.

However, by the 2010s, it would come to be perceived as disrupting the urban fabric of riverfront neighborhoods while effectively disconnecting the Connecticut River, the Connecticut River Walk Park and the Naismith Memorial Basketball Hall of Fame from everything east of the highway—the majority of the city.

I-91 was erected without tunnels, footbridges or other paths, a design choice which poses logistical problems for travel between the riverfront and the remainder of the city.

The placement of I-91 has left Springfield's riverfront virtually undeveloped, aside from the sliver of land surrounding the Basketball Hall of Fame.

Springfield's most popular tourist attraction, the riverfront Basketball Hall of Fame, is separated from Metro Center by a 20-foot (6.1 m) stone wall, buttressing an elevated portion of the six-lane I-91 and greatly discouraging travel between the two areas.

[39] The extension would have continued southward from Wading River to the southern shore of Long Island by the existing County Route 46 (William Floyd Parkway) in central Suffolk County—which would have been updated to Interstate Highway standards.

[48] In 2000, a survey was conducted by News 12 Networks and Newsday, which found that the majority (63 percent) of Long Islanders were in support of such a project.