Spanning approximately 21 miles (34 km) along a south–north axis, it is a continuation of Rhode Island Route 146, which splits from I-95 in Providence.

The southern terminus within Massachusetts exists in Millville, where it enters the state from North Smithfield, Rhode Island.

Most of the route is a freeway, except for a short section near the boundary between Millbury and Sutton where there is driveway access and at-grade crossings.

During the late 1940s, the then-Massachusetts Department of Public Works (MassDPW, now MassDOT) planned an extension of Route 146 from Rhode Island north toward Worcester.

The project upgrading the section linking Exit 94 on the Massachusetts Turnpike north into downtown Worcester at Brosnihan Square to Interstate Highway standards was completed in November 2007 according to MassHighway.

Lydia Chapin Taft's historic vote and her role in the history of Women's suffrage is recognized by the Massachusetts legislature since 2004, which named Route 146A from Uxbridge to the Rhode Island border in her honor.