In Maryland, U.S. Route 1 runs between Washington, DC and Baltimore parallel to Interstate 95, before turning away from I-95 north of Baltimore and forging its own path into Pennsylvania. Before the construction of local Interstate highways, US 1 was the main north-south through route between Baltimore and DC.

US 1 has its own business route through Bel Air in Harford County and a Susquehanna River crossing via the Conowingo Dam.