U.S. Route 64 (US 64) is the longest numbered route in the U.S. state of North Carolina, running 604 miles (972 km) from the Tennessee state line to the Outer Banks. The route passes through the westernmost municipality in the state, Murphy, and one of the most easternmost municipalities, Manteo, making US 64 a symbolic representation of the phrase "from Murphy to Manteo" which is used to refer to the expanse of the state. The highway is a major east–west route through the central and eastern portion of the state.

The Outer Banks are a 200 mi (320 km) string of barrier islands and spits off the coast of North Carolina and southeastern Virginia, on the east coast of the United States. They line most of the North Carolina coastline, separating Currituck Sound, Albemarle Sound, and Pamlico Sound from the Atlantic Ocean. A major tourist destination, the Outer Banks are known for their wide expanse of open beachfront and the Cape Hatteras National Seashore. The seashore and surrounding ecosystem are important biodiversity zones, including beach grasses and shrubland that help maintain the form of the land.