Lawrence lies along Interstate 495, which passes through the eastern portion of the city. There are three exits that are totally within the city, while two more provide access from a small area just beyond the city. The town is also served by Route 28, which runs through it from south to north, and Route 110, which runs through the northern portion of the city from east to west. Route 114 also has its western terminus at Route 28 at the Merrimack River. Lawrence is the site of four road crossings and a railroad crossing over the Merrimack, including the O'Leary Bridge (Route 28), a railroad bridge, the Casey Bridge (bringing Parker Street and access to Route 114 and the Lawrence MBTA station to the north shore), the Duck Bridge (which brings Union Street across the river), and the double-decked O'Reilly Bridge, bringing I-495 across the river.

Lawrence is the western hub of the Merrimack Valley Regional Transit Authority's bus service. It is also home to the Senator Patricia McGovern Transportation Center, home to regional bus service and the Lawrence stop along the Haverhill/Reading Line of the MBTA Commuter Rail system, providing service from Haverhill to Boston's North Station. Amtrak's Downeaster service to Maine is available eight miles to the northeast in Haverhill. Lawrence Municipal Airport provides small plane service, though it is actually in neighboring North Andover. Lawrence is approximately equidistant from Manchester-Boston Regional Airport and Logan International Airport.