From 1962 to 1976, Route 51 was the number for today's inland section of the Post Road (US 1), from Old Lyme to East Lyme. Its alignment, from west to east:

• Halls Road, from Route 156 to Lyme St; this was formerly part of Route 156A
• Lyme St, to the Boston Post Road (now US 1)
• Boston Post Road, to I-95 in East Lyme

Since the 1930s, this portion of road had been part of US 1. In late 1949, a new 8.4-mile section of relocated US 1 opened between the Baldwin Bridge over the Connecticut River at Old Lyme, and a point in East Lyme east of Route 161. This new highway was 2 lanes wide with access controlled by interchanges; in other words, a "Super 2". The state designed the route with plans for future expansion; today, it's part of I-95.

When US 1 moved to the new highway, Boston Post Road to the north reverted to town maintenance. In 1958, when I-95 was designated, it shared this section of highway with US 1.

As a result of the state's road reclassification effort in 1961, the Boston Post Road was taken back into the state highway system. In 1962, this road was given a new designation: Route 51.

It evidently occurred to someone, however, that having three designations (Route 51, US 1, I-95) for two parallel roads was not necessary. In 1976, US 1 was returned to the Boston Post Road. I-95 became the sole designation for the freeway. The Route 51 designation, no longer needed, was removed.