The bay is the largest inlet in the Atlantic coastal plain.

The first European settlement in the bay was Jamestown, founded in 1607.

A naval battle was fought at the mouth of the Chesapeake Bay between the French fleet under Admiral de Grasse and the British relief fleet under Admiral Thomas Graves. The British were driven away. The French fleet then controlled the bay, cutting off all aid to Cornwallis and his troops who were now surrounded by American and French forces at Yorktown.