The name derives from a word from a Native American language that means "land between two waters."

Nassawadox is bounded on the east by the Atlantic Ocean and on the west by the Chesapeake Bay.

The racial makeup of the town was 54.90% African American, 43.18% White, 0.87% Asian, and 1.05% from two or more races.

The Bay Coast Railroad provided Nassawadox with freight rail service until going out of business in 2018.

The climate in this area is characterized by hot, humid summers and generally mild to cool winters.