The road winds through the communities of Atkinson, Hampstead, Sandown, Derry, Chester, and Auburn.

The southern terminus of NH 121 is at the Massachusetts state line in Plaistow, where the road, named Atkinson Depot Road, continues into the city of Haverhill as an unnumbered local road (North Main Street) leading to Route 125.

The northern terminus is at a traffic circle, where NH 121 meets New Hampshire Route 28 Bypass (the Londonderry Turnpike) in eastern Manchester.

The southern terminus of NH 121A is at the Massachusetts state line in Plaistow, where the road continues for approximately 87 yards (80 m) into Massachusetts before ending at Massachusetts Route 125, a continuation of New Hampshire Route 125 in Haverhill.

The northern terminus of NH 121A is in the town of Chester at New Hampshire Route 121.