U.S. Route 301 (US 301) in the state of Maryland is a major highway that runs 122.85 miles (197.71 km) from the Governor Harry W. Nice Memorial Bridge over the Potomac River into Virginia northeast to Delaware.

[1] Robert Crain was a Charles County farmer and lawyer who spearheaded the construction of a new highway to directly connect Baltimore and Southern Maryland that was completed in 1927.

The highway parallels CSX's Popes Creek Subdivision rail line on a sweeping curve from east to north through the community of Newburg.

The highway curves northwest at its directional crossover intersection with MD 234 (Budds Creek Road) at the hamlet of Glasva, then curves north again between Faulkner and Bel Alton, from which Chapel Point Road leads west to Chapel Point State Park.

US 301 expands to six lanes near Smallwood Drive, where it passes south of a park and ride lot serving MTA Maryland commuter buses.

The highway continues through Marlton, where it crosses Charles Branch and meets the northern end of MD 382 (Croom Road).

The highway continues north, passing a pair of weigh stations, and gains a wide median at the southern edge of the city of Bowie.

US 301 follows the eastern city limit of Bowie and expands to six lanes south of its intersection with MD 197 (Collington Road).

[1][7] US 301 and US 50 head east along John Hanson Highway, a six-lane freeway, across the Patuxent River into Anne Arundel County.

The six-lane freeway parallels MD 18 and has numerous right-in/right-out interchange with local roads as it passes through Stevensville and Chester.

US 301 and US 50 parallel MD 18 across the Kent Narrows onto the mainland of the Delmarva Peninsula, then the freeway continues through more right-in/right-out interchanges in Grasonville before the U.S.

[1][7] US 301 reduces to a four-lane non-freeway divided highway with a speed limit of 55 miles per hour (89 km/h) at its partial interchange with US 50 (Ocean Gateway).

US 301 has a four-ramp partial cloverleaf interchange with MD 290 (Dudley Corner Road) just south of Red Lion Branch.

The highway meets the northern end of MD 299 (Massey Sassafras Road), where there is a weigh station in the southbound direction, and passes to the south of Warwick.

US 301 reaches the Maryland–Delaware state line, where it continues northeast into New Castle County along an all-electronic toll freeway.

By the late 1980s, the segment of the highway between the Chesapeake Bay Bridge and the US 50/US 301 split in Queenstown still a four-lane at-grade divided expressway, was extremely congested.

A groundbreaking ceremony was held on September 23, 2014, with several Queen Anne's County commissioners and representatives from state government in attendance.

[14] The Pearl Harbor Memorial bridge was expanded to seven lanes, four eastbound and three westbound, from the fall 2017 to the spring of 2018.

The Maryland Transportation Authority has been studying the twinning or replacement of the Harry W. Nice Memorial Bridge over the Potomac River since about 2006, and identified a preferred alternative which involved replacing the two-lane span with a new bridge with four lanes, shoulders and a new two-way bike and pedestrian trail.

[15] On November 21, 2016, the Maryland Transportation Authority Board voted unanimously to build a new four-lane bridge just north of the current structure.

[18] Between September 16, 2023, and October 1, 2023, a pilot project took place in which the westbound entrances at MD 8, Duke Street, and Shopping Center Road on Kent Island were closed from 10 a.m. to 8 p.m. on Saturday and Sunday in order to keep through traffic approaching the Chesapeake Bay Bridge on US 50 and reduce traffic along MD 18.

In December 2004, plans were announced on a project to potentially replace the Chesapeake Bay Bridge with a new six lane span.

Significant environmental and economic impacts were identified, with a report stating that any additional crossing is "expected to be multiple billions of dollars.