Route 146 begins in Branford as Main Street, splitting off from West Main Street (US 1) just east of the connector road to I-95 at Exit 53. It heads east towards Branford Center and shifts to South Main Street as it passes behind the Branford Green. At the end of the street, Route 146 turns south onto Montowese Street, becoming South Montowese Street and Sybil Avenue as it proceeds southward towards the Indian Neck section of the town at the shore of Long Island Sound. The road then bears east along the shore as Limewood Avenue, Hotchkiss Grove Road, Elizabeth Street, and Pine Orchard Road, heading into the Pine Orchard section of town. At Pine Orchard, Route 146 turns north onto Blackstone Avenue and Totoket Road. The road then takes a sharp eastward turn at Stony Creek Road then heads east and south onto Leetes Island Road. Leetes Island Road crosses into the town of Guilford, bears north briefly on Sachem Head Road, then northeast onto Water Street, passing on the south side of the Guilford Town Green as Boston Street, eventually terminating at US 1 east of the town center.