The Neuse River originates northwest of Durham and flows southeasterly for over 200 miles past Raleigh, Smithfield, Goldsboro, Kinston, and New Bern to the tidal waters of the Pamlico Sound. It encompasses 6,192 square miles in 19 counties. It is the third largest river basin in North Carolina and is one of three major basins whose boundaries are located entirely within the state. This river provides habitat for a number of important migratory fish, including striped bass, American and hickory shad, alewife, blueback herring, two species of sturgeon, and American eel.

The Neuse River has the widest mouth of any river in the continental US and is part of the second largest estuarine system in the states.