Route 129 begins at Route 110 in Chelmsford Center, where the northbound lanes of Route 4 leave Route 110. The route passes out of the town center to the east before intersecting U.S. Route 3 at Exit 29. It passes into Billerica, and shortly thereafter has a concurrency with Route 3A for just over a mile, following southbound on that route and crossing the Concord River. The route then turns eastward once more, heading over the Shawsheen River into Wilmington. In Wilmington, Route 129 becomes concurrent with Route 38, crossing Route 62 and passing the Wilmington MBTA station in the process. The two routes split south of the intersection, with Route 129 heading more southeasterly towards its intersection with Interstate 93 at Exit 38.