Route 121 begins at an intersection with US 1 in Milford and heads north, passing underneath I-95 without a junction 0.3 miles (0.48 km) later, then enters the town of Orange after another 1.5 miles (2.4 km).

In Orange, Route 121 continues north, intersecting about half a mile later with Derby-Milford Road, a direct route into Derby, and the Wilbur Cross Parkway (Route 15) at Exit 56 after another 1.6 miles (2.6 km).

The road continues past the Wilbur Cross Parkway for another 1.6 miles (2.6 km) until the intersection with Route 34 (Derby Turnpike) in the northern edge of Orange, where Route 121 ends.

In Milford, Route 121 is known as North Street, while in Orange, it is known as Grassy Hill Road.

In 1941, Route 121 was shortened when US 1 was relocated from Cherry Street to its current route at the Boston Post Road.