It runs 2,370 miles (3,810 km) from Key West, Florida, north to Fort Kent, Maine, at the Canadian border, making it the longest north–south road in the United States.

[2] US 1 is generally paralleled by Interstate 95 (I-95), though US 1 is significantly farther west and inland between Jacksonville, Florida, and Petersburg, Virginia, while I-95 is closer to the coastline.

US 1 travels along the east coast of Florida, beginning at 490 Whitehead Street in Key West[5] and passing through Miami, Hollywood, Fort Lauderdale, Boca Raton, West Palm Beach, Jupiter, Fort Pierce, Melbourne, Cocoa, Titusville, Daytona Beach, Palm Coast, St. Augustine, and Jacksonville.

The southernmost piece through the chain islands of the Florida Keys, about 100 miles (160 km) long, is the two-lane Overseas Highway, originally built in the late 1930s after railroad tycoon Henry Flagler's Florida East Coast Railway's Overseas Railroad, which was built between 1905 and 1912 on stone pillars, was ruined by the 1935 Labor Day hurricane.

Famous vacation scenic route State Road A1A is a continuous oceanfront alternate to US 1 that runs along the beaches of the Atlantic Ocean, cut only by assorted unbridged inlets and the Kennedy Space Center at Cape Canaveral.

Starting in South Carolina, US 1 is paralleled by I-20 along the Atlantic Seaboard Fall Line through Aiken, Lexington, and Columbia to Camden and Lugoff.

US 1 runs concurrently with US 64 through most of Cary, where the freeway recently underwent a major renovation and improvements that added lanes in both directions.

[8] North of Raleigh, US 1 (known as Capital Boulevard in northern Wake County) crosses I-540 and then again becomes a four-lane divided arterial to I-85 near Henderson.

US 1 is at the minimum of three lanes (with alternate passing) from the North Carolina state line to Petersburg with occasional four-lane divided sections.

After exiting DC into Maryland, US 1 follows the Baltimore–Washington Boulevard, the first of several modern highways built along the Washington–Baltimore combined statistical area corridor; I-95 is the newest, after the Baltimore–Washington Parkway.

The route bypasses Downtown Baltimore on North Avenue and exits the city to the northeast on Belair Road, gradually leaving the I-95 corridor, which passes through Wilmington, Delaware, for a straighter path toward Philadelphia.

Around and beyond Bel Air, US 1 is a two-lane road, crossing the Susquehanna River over the top of the Conowingo Dam before entering Pennsylvania.

US 1 again becomes a freeway after leaving the city, bypassing Penndel and Morrisville and crossing the Delaware River into New Jersey on the Trenton–Morrisville Toll Bridge.

As the freeway ends, the four-lane divided highway upgrades to six lanes north of I-295 passing through the Penns Neck section of West Windsor.

The New Jersey Department of Transportation (NJDOT) is looking to revamp the highway through this area by replacing traffic signals with grade separations.

The highway enters Middlesex County through Plainsboro Township and South Brunswick, where the highest point resides.

Northward, it continues through New Brunswick as a short limited-access highway until the County Route 529 (CR 529)/Plainfield Avenue traffic signal in Edison.

The historic Pulaski Skyway takes US 1/9 into Jersey City, and the route exits the freeway at the Tonnele Circle to head north into Bergen County.

While I-95 in Rhode Island takes a diagonal path to Providence, US 1 continues east along the coast through Westerly to Wakefield-Peacedale, where it turns north and follows Narragansett Bay.

The Tobin Bridge and Northeast Expressway take US 1 out of Boston, after which it again parallels I-95 as a high-speed surface road through Newburyport to the New Hampshire state line.

[6] The short portion of US 1 in New Hampshire follows the historic Lafayette Road, staying close to I-95, passing through Portsmouth before crossing the Piscataqua River on Memorial Bridge, which was demolished and replaced during 2012–2013, leaving a temporary gap in US 1.

[15] Due to the overlapping of auto trail designations, portions of the route had other names that remain in common use, such as the Boston Post Road between Boston and New York City, the Lincoln Highway between New York and Philadelphia, the Baltimore Pike between Philadelphia and Baltimore, and the Dixie Highway in and south of eastern Georgia.