Panama Passage is the story of Harry Kellems, a young engineer, whose wealthy, spoiled, and pampered wife decided to join him in plague-ridden, rudimentary Panama. Panama, in those days, was no place for a sheltered woman, but with the help of Colonel Gorgas, who valued Kellems as a loyal worker, the young couple managed to find not-too-bad quarters.

On the boat which brought her to Panama, Phil met and became attracted to Captain Ward Wright, a romantic-looking soldier of fortune in the pay of those interested in blocking the construction of the Panama Canal. He was an exciting contrast to her young and naive husband.

But perhaps Harry was not so naive as he seemed, for he himself had meanwhile fallen more than half in love with Madeline Desmoulins, the pretty and aristocratic daughter of a wealthy old Frenchman.

Out of this situation grows the action and suspense of the story. Always in the background, and lending scope and importance to the novel, is the panorama of the great canal venture and the reclaiming of the mosquito-cursed land.