U.S. Route 5 (US 5) is a part of the United States Numbered Highway System that runs from New Haven, Connecticut, to the Canada–United States border at Derby Line, Vermont. In Vermont, the road runs south–north from the Massachusetts state line near Guilford to the international border. The 192.317 miles (309.504 km) that lie in Vermont are maintained by the Vermont Agency of Transportation (VTrans) and run largely parallel to Interstate 91 (I-91). US 5 also follows the path of the Connecticut River from the Massachusetts border to St. Johnsbury, where the river turns northeast while US 5 continues north. The highway serves the major towns of Brattleboro, Hartford, and St. Johnsbury, along with the city of Newport near the Canadian border.

St. Johnsbury is the shire town of Caledonia County, Vermont, United States. As of the 2020 census, the population was 7,364. St. Johnsbury is situated on the Passumpsic River and is located approximately six miles northwest of the Connecticut River and 48 miles (77 km) south of the Canada–U.S. border.