The road runs from its origin in Lowell, Massachusetts to its northern end in Hooksett, New Hampshire, a suburb of Manchester.

This is located on the south bank of the Merrimack River, and near the campus of the University of Massachusetts Lowell.

The road proceeds to cross over the river on the O'Donnell Bridge, and immediately intersects Route 113 (Riverside Street, Varnum Avenue), which leads to Tyngsboro in the west and Lawrence in the east.

Mammoth Road becomes New Hampshire Route 128 (NH 128), and enters the town of Pelham, which is in Hillsborough County.

After passing under this, South Mammoth Road travels through the eastern side of downtown Manchester.

Once through these intersections, the road meets up with Bridge Street, which is a major east-west throughfare connecting to the center of downtown Manchester and I-93.