Massachusetts Route 10 is a north–south state highway that runs from the state line at Southwick to the state line at Northfield.

Route 10 crosses the border from Granby, Connecticut into Southwick, Massachusetts, overlapped with US 202. It runs north through the Pioneer Valley towns of Southwick, Westfield, Southampton, Easthampton, Northampton, Hatfield, Whately, Deerfield, Greenfield, Bernardston, Gill, and Northfield. Route 10 has a long concurrency with U.S. Route 5 for about 25 miles (40 km) from Northampton to Bernardston, where it was sometimes called the "5 & 10 Highway". During this concurrency, it closely parallels Interstate 91, with five exits from Northampton to Deerfield, with close access at Route 2 in Greenfield and another exit, solely for Route 10, in Bernardston. It crosses the Connecticut River in Northfield before entering New Hampshire. Route 10 is concurrent with seven other routes (US 5, US 20, US 202, and Massachusetts Routes 57, 9, 116 and 63) for 43 of its nearly 61 miles in the state with three points of triple concurrency, leaving less than a third of its length as the sole road designation.

An odd sight greeted motorists in Easthampton in July, 2005: standard issue Alabama state highway signs with the number 10 in a map of that state, instead of the standard Massachusetts square. This odd "Alabama 10" signage came about when a contractor mistakenly applied the sample from a federal manual.