Old Crain Highway splits north from US 301 as the highway approaches Upper Marlboro, the county seat of Prince George's County. The U.S. Highway curves north and crosses CSX's Popes Creek Subdivision rail line at-grade and heads across the Western Branch of the Patuxent River south of its cloverleaf interchange with MD 4 (Stephanie Roper Highway). US 301 meets the eastern end of MD 725 (Marlboro Pike) east of Upper Marlboro.
Old Crain Highway branches off from US 301 as it approaches Upper Marlboro, the county seat of Prince George's County. The highway curves north and crosses CSX's Popes Creek Subdivision rail line at ground level before heading south across the Western Branch of the Patuxent River near its cloverleaf interchange with MD 4 (Stephanie Roper Highway). US 301 meets the eastern end of MD 725 (Marlboro Pike) east of Upper Marlboro.