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Along the Outer Banks, navigational challenges posed by the Diamond Shoals area off Cape Hatteras, caused the loss of thousands of ships and an unknown number of human lives. More than 5,000 ships have sunk in these waters since record-keeping began in 1526. The Graveyard of the Atlantic Museum, located in Hatteras Village, focuses on the history of this area and features many artifacts recovered from area shipwrecks.

Among the better known shipwrecks were the USS Monitor, a participant in the famous Battle of Hampton Roads during the American Civil War, and the Patriot which carried Theodosia Burr Alston, Aaron Burr's daughter. The Monitor foundered and sank on December 31, 1862, off Cape Hatteras, while the Patriot presumably sank off the coast in January 1813. The first recorded shipwreck off the coast of North Carolina was in 1526 off the mouth of Cape Fear River. The large numbers of explorers who came to the area in subsequent years had to travel through the rough waters to get to the coast of North Carolina. In June 1718, Edward Teach—better known as Blackbeard the pirate—ran his flagship, the Queen Anne's Revenge, aground near present-day Beaufort Inlet, NC. Thirty-two years later, in August 1750, at least three Spanish merchantmen ran aground off North Carolina during a hurricane: the El Salvador sank near Cape Lookout, while the Nuestra Señora de Soledad went ashore on near present-day Core Banks, and the Nuestra Señora de Guadalupe went ashore near present-day Ocracoke Island. Survivors of a much earlier shipwreck created the lost town of Wash Woods, Virginia using lumber that washed ashore. However, the extreme weather eventually claimed the town as well.

During World War II, German U-boats would sit offshore and prey on passing freighters and tankers silhouetted against the lights onshore. Hundreds of ships along the North Carolina coast were torpedoed by submarines in this fashion in what became known as Torpedo Alley. In the twenty-first century, ships still have trouble in the area including the Bounty which sank off Cape Hatteras in 2012 due to Hurricane Sandy and a 72-foot fishing boat called the Ocean Pursuit which ran aground on Bodie Island in 2020.