In Rhode Island, Route 121 exists entirely in a rural section of Cumberland.

It proceeds for 1 mile (1.6 km) from an intersection with Route 114 along Wrentham Road to the Massachusetts State line.

Now in Wrentham, Massachusetts, the road proceeds for 4.4 miles (7.1 km) to an intersection with Route 1A.

In the mid-1960s, the southern end of the route was truncated by about 5.4 miles (8.7 km) to its current southern terminus at the intersection of Pine Swamp Road and Diamond Hill Road in Cumberland.

This was due to the westward extension of the Route 114 designation into the city of Woonsocket.