Route 150 begins at an intersection with Beacon Street, an unusual instance that a numbered route does not have its terminus with another numbered route. Less than a half mile north is the intersection with Interstate 495 at Exit 54, which is the first exit on the southbound side of the interstate. Route 150 intersects with Route 110 (Haverhill Road) about one-quarter mile further north. After this intersection, Route 150 then becomes the primary thoroughfare through the center of the city, passing through the more densely populated and commercialized downtown of Amesbury. During this section, the road splits for about one-quarter mile into two one-way segments, with the northbound and southbound sides carrying traffic through different parts of downtown before rejoining together. This one-way southbound route passes through a roundabout and shortly after the two sides rejoin, the two-way road passes through another roundabout. After travelling through downtown Amesbury the road reaches the more rural northern section of the city and then crosses into South Hampton, New Hampshire. The highway becomes New Hampshire Route 150 upon crossing the state line.