Interstate 90 (the Massachusetts Turnpike), which runs east-west along the Town's southern boundary, is the primary mode of regional transit. The closest Turnpike entrance/exit is in adjacent Framingham, approximately southwest of Lake Cochituate. Wayland also provides excellent access to Boston's inner and outer circumferential freeways, with I-95/Route 128 two miles east and I-495 ten miles west. Boston Post Road (Route 20) runs east-west through the center of town, while Routes 27 and 126 (which overlap for a time in the center of town) go north-south. Route 30 gives access to the east and is frequently used to bypass the Mass Pike and connect to Interstate 95.

Routes 20, 27, 30, and 126 are the primary routes that go through Wayland and connect it to the surrounding communities. Each of these routes has paths/walkways on at least one side of the road. These primary routes allow access to lesser rural roads and residential streets across the rest of the Town.

While Wayland does not have a commuter rail station, there are stations in nearby communities. MBTA commuter rail travels to Boston's North Station through the Fitchburg Line (in Weston and Lincoln) and to Boston's South Station via the Worcester Line (in Framingham, Natick, and Wellesley).