Massachusetts Route 10 is a 60.69-mile-long (97.67 km) north–south state highway that runs from the Connecticut state line at Southwick to the New Hampshire state line at Northfield. Originally part of New England Route 10 from 1922 to 1927, it continues to the south as Connecticut Route 10, and to the north as New Hampshire Route 10.

Route 10 crosses the border from Granby, Connecticut into Southwick, Massachusetts, overlapped with U.S. 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. 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 miles (69.20 km) of its nearly 61 miles (98.17 km) 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. The signs have since been replaced with the correct shields.

County	Location	mi	km	Destinations	Notes
Hampden	Southwick	0.0	0.0	US 202 south / Route 10 south – Salmon Brook	Continuation into Connecticut
		1.9	3.1	Route 168 east – West Suffield, CT, Suffield, CT	Western terminus of Route 168
		4.3	6.9	Route 57 west – Granville, New Marlborough	Southern terminus of concurrency with Route 57
		4.9	7.9	Route 57 east – Feeding Hills, Springfield	Northern terminus of concurrency with Route 57
	Westfield	9.6	15.4	US 20 east – Springfield, Palmer	Southern terminus of concurrency with US 20
		9.9	15.9	US 20 west – Russell, Pittsfield	Northern terminus of concurrency with US 20
		11.3	18.2	I-90 / Mass Pike – Boston, Albany, NY	Exit 41 on I-90 / Mass Pike
		14.3	23.0	US 202 north – Holyoke, Belchertown	Northern terminus of concurrency with US 202
Hampshire	Easthampton	21.8	35.1	Route 141 east – Holyoke	Western terminus of Route 141
	Northampton	26.1	42.0	Route 9 west – Williamsburg, Pittsfield	Southern terminus of concurrency with Route 9
		26.4	42.5	Route 9 east / US 5 south – Amherst, Worcester, Holyoke, Springfield	Northern terminus of concurrency with Route 9; southern terminus of concurrency with US 5
		27.8	44.7	I-91 north – Greenfield, Brattleboro, VT	Exit 26 on I-91; northbound exit and southbound entrance
		29.6	47.6	I-91 – Springfield, Brattleboro, VT	Exit 27 on I-91; northbound access via Elm Street
	Hatfield	32.0	51.5	I-91 south – Holyoke, Springfield	Exit 30 on I-91
		32.3	52.0	I-91 north – Greenfield, Brattleboro, VT	Exit 30 on I-91
Franklin	Whately	34.0	54.7	I-91 north – Greenfield, Brattleboro VT	Exit 32 on I-91; northbound entrance
		34.7	55.8	I-91	Exit 32 on I-91; entrance from I-91 south
		37.1	59.7	I-91 south – Holyoke, Springfield	Exit 35 on I-91
		37.4	60.2	Route 116 south – Sunderland, Amherst	Southern terminus of concurrency with Route 116
	Deerfield	38.3	61.6	Route 116 north to I-91 north – Conway, Ashfield	Northern terminus of concurrency with Route 116
	Deerfield River	44.6	71.8	Deerfield River Bridge
	Greenfield	46.0	74.0	Route 2A – Athol	Court Square, site of historic road marker
		47.7	76.8	Route 2 to I-91 – Boston, North Adams	Interchange
	Bernardston	52.5	84.5	US 5 north – Brattleboro VT, White River Jct., VT	Northern terminus of concurrency with US 5
		52.9	85.1	I-91 – Greenfield, Springfield, Brattleboro, VT, White River Jct., VT	Exit 50 on I-91
	Gill	55.5	89.3	Route 142 north – Northfield, Vernon, VT	Southern terminus of Route 142
	Connecticut River	56.8	91.4	Bennett's Meadow Bridge
	Northfield	57.5	92.5	Route 63 south – Millers Falls, Amherst	Southern terminus of concurrency with Route 63
		59.9	96.4	Route 63 north – Hinsdale, NH	Northern terminus of concurrency with Route 63
		60.7	97.7	NH 10 north – Keene	Continuation into New Hampshire
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus       Electronic toll collection       Incomplete access

• New England Interstate Route 10

• Route 10 endpoint photos