It runs near the Connecticut River throughout its journey in Chicopee, crosses into Holyoke, and abruptly ends at High Street 0.4 miles (0.64 km) south of U.S. Route 202 (US 202).

I-391 continues north through the rest of northern Chicopee, intersecting Route 141 along the way and then passing just east of Rivers Park.

I-391 then crosses the Connecticut River into the city of Holyoke, where it has two closely spaced exits for local streets in the town.

I-391 officially comes to an end at High Street in Holyoke, with the road continuing as Resnic Boulevard, which connects to US 202 after 0.4 miles (0.64 km).

By the 1960s, freeway access was needed between Chicopee and Holyoke to improve traffic flow which prompted a spur route of I-91 to be built.