Route 128 is a ring highway with Boston at its center and surrounded by the concentric Interstate 495. It runs concurrently with Interstate 95 from Canton to Peabody, and when I-95 continues north from Peabody, 128 runs east from Peabody to Gloucester. Until 1997, it also ran concurrently with the present Interstate 93 from Canton to Braintree; that stretch of Interstate 93, though no longer officially part of Route 128, is still often referred to as "Route 128" by locals. The entire highway from Braintree up to Gloucester has the official name The Yankee Division Highway.

Route 128 was one of the first limited-access highways in the United States.

Also known as the high-tech corridor, the area along the western part of Route 128 is home to a number of high-technology firms and corporations.

Route 128 makes more than a 180-degree arc around Boston, and clockwise is "north" even when the road heads slightly south of east when approaching the Atlantic Ocean. Hackers in the area refer to this as going "logical north" on the route. (Interstate 93, going north-and-south, intersects Route 128, which nominally goes north-and-south, at a right angle, about 15 miles north of Boston. Moreover, when I-93 and Route 128 ran concurrently south of Boston, before 1997, they were signed in opposite directions, so it was possible to travel north on I-93 and south on Route 128 at the same time.)

Route 128 Station is located along the highway in Westwood, Massachusetts and is served Amtrak's Northeast Corridor line and MBTA commuter rail.

Route 128 has also been mentioned in several rock and roll songs such as "Blue Thunder" by Galaxie 500 and the road anthem "Roadrunner" by Jonathan Richman & the Modern Lovers.