Two shiploads of hopeful colonists arrive on the rugged coast of present day Maine in late spring, 1607. They are determined to establish Popham Colony as a permanent English presence, just as other English settlers were doing farther south at the Jamestown settlement. By diligent effort, they construct a substantial fort, Fort St. George, to serve as their "base."

What these intrepid adventurers cannot know is that one of their number, Duke Esteban Menendez, has actually been recruited by the King of Spain as a spy to ensure that this British effort fails. Betrayal at Popham traces the efforts of this dedicated nobleman in his own words, from settlement of Popham Colony to its final abandonment. Adding a touch of romance to this tale of intrigue and betrayal is the tender relationship that develops between one of the Popham settlers, young Reggie Patterson, and the beautiful Abenaki Indian maiden, Angelique.