Pamlico Sound in North Carolina, is the largest lagoon along the U.S. East Coast, being 129 km (80 mi) long and 24 to 48 km (15 to 30 miles) wide. It is a body of water separated from the Atlantic Ocean by the Outer Banks, a row of low, sandy barrier islands, including Cape Hatteras. The Neuse and Pamlico rivers (the latter is the estuary of the Tar River) flow in from the west. Pamlico Sound is linked on the north with Albemarle Sound through Roanoke Sound and Croatan Sound (passages). Core Sound is the narrow southern end.

Explorer Giovanni da Verrazzano mistook the sound for the Pacific Ocean. The sound and its ocean inlets are noted for wide expanses of shallow water and occasional shoaling, making the area hazardous for larger vessels. In addition, the shallow waters are susceptible to wind and barometric pressure-driven tidal fluctuations. This effect is amplified on the tributary rivers, where water levels can change by as much as two feet in three hours when winds are aligned with the rivers' axes and are blowing strongly.

Pamlico Sound is part of a large, interconnected network of lagoon estuaries. As a whole it is the second largest estuary in the United States (Chesapeake Bay is the largest). Seven sounds making up the whole: Albemarle Sound, Currituck Sound, Croatan Sound, Pamlico Sound, Bogue Sound, Core Sound, and Roanoke Sound.

Cape Hatteras National Seashore and Cape Lookout National Seashore are located on the barrier islands. Along the coastal areas are numerous waterfowl nesting sites, including Pea Island National Wildlife Refuge and Swanquarter National Wildlife Refuge on the mainland.

The Albemarle-Pamlico Sound is one of nineteen great waters recognized by the America's Great Waters Coalition.

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