Three exits provide access to Methuen, which is located at the northernmost point of Interstate 93 in Massachusetts. From Lawrence to Haverhill, a section of Interstate 495 passes across the town's eastern side. With three intermediary exits of its own in addition to the exits for I-93 and I-495, Massachusetts Route 213, known as the "Loop Connector," gives access to the two from the freeway. The town is also crossed by Route 28, Route 110, and Route 113, the latter two meeting at I-93 Exit 43 (old exit 46). I-93 provides the town's only bridge across the Merrimack; there are several crossings in Lawrence, and several in neighboring Haverhill, but none for 7 miles (11 km) upstream from I-93 all the way to the eastern end of Lowell.

Methuen is served by the Merrimack Valley Regional Transit Authority's bus service. From the Methuen Park and Ride, OurBus offers daily intercity bus service to Worcester and New York City. The closest rail station is in South Lawrence, which is a stop on the MBTA Commuter Rail's Haverhill/Reading Line that runs into Boston's North Station. Small plane service can be found at Lawrence Municipal Airport and the Merrimack Valley Seaplane Base, with the nearest national service being at Manchester-Boston Regional Airport, and the nearest international service being at Logan International Airport.