Within the narrative framework of the novel, Captain Paxton, United States Army Infantry, is a fan of Burroughs' Barsoom series, and after having a shell blow off his legs during trench warfare in World War I, he finds himself drawn across the gulfs of space to Mars (where his body is whole again) like John Carter before him.

[2] On Mars, Paxton is taken in by elderly mad scientist Ras Thavas, the "Master Mind" of the novel's title, who educates him in the ways of Barsoom and bestows on him the Martian name Vad Varo.

Ras has perfected techniques of transplanting brains, which he uses to provide rich elderly Martians with youthful new bodies for a profit.

But Paxton has fallen in love with Valla Dia, one of Ras' young victims, whose body has been swapped for that of the hag Xaxa, Jeddara (empress) of the city-state of Phundahl.

A quest for that body ensues, in which Paxton is aided by others of Ras' experimental victims, and in the end (and after meeting fellow Earthman John Carter) he attains the hand of his Valla Dia, who in a happy plot twist turns out to be a princess.