Betty Marsh, along with her friend, Henrietta McCoy, and archaelogists Cleary, Fronc, Brewster and Coggins, attempts to hire a guide at Rutledge's trading post so that they can find Betty's father, who disappeared three months earlier while searching for the lost Indian city of Luckachakai. The Three Mesquiteers--Stony Brooke, Tucson Smith and Lullaby Joslin--arrive at the trading post with Professor Faxon, Marsh's companion, whom they found wandering in the desert. Faxon rambles incoherently about a whistling skull and the city of gold, and warns Betty that she must rescue her father before he is tortured by his captors. Faxon is stabbed before he can reveal more about the mystery, and as the sheriff does not have sufficient evidence to hold them, Betty, her companions, the Mesquiteers and Rutledge and his Indian guide Otah set off in search of Marsh. They argue over who will keep Marsh's notebook, which contains a map to the whistling skull, and although only Betty can read the Indian hieroglyphics her father wrote in, Tucson suggests splitting the map up among all of them. Soon after they leave, Cleary is killed by a mysterious arrow inscribed with the same writing that was on the knife that killed Faxon. The Mesquiteers then discover that Cleary's piece of the map is missing. The discouraged group makes camp for the night, and when they set off in the morning, they find Fronc wandering in the desert after he has been branded by the members of an Indian cult, the Sons of Anatazia. Fronc's piece of the map is gone, and while Rutledge, Brewster and Coggins wish to turn back, Betty insists on going forward. After they begin again, the mysterious Indians spook some of the horses, who run wild. Tucson and Stony retrieve the horses, but Betty is kidnapped by the Indians in the confusion. The Mesquiteers follow the trail left by the kidnappers and soon rescue Betty, after which, the group presses onward. While following Otah and Rutledge, Stony and Tucson find water and then the whistling skull rock formation. The group takes refuge in the cave of the skull when the Indians, led by the half-breed Rutledge, attack them. They then find Marsh, who tells them that Rutledge has kept him prisoner for not revealing the location of the treasure of Luckachakai. The Mesquiteers leave the cave to get help, but Stony is captured and held hostage. Before Stony can be sacrificed, however, Tucson finds the sheriff, who has been following them with a posse in case they needed help, and they rescue Stony. Rutledge and his men are buried in an avalanche, and later, Tucson happily reads his detective magazine, while Henrietta admires Lullaby's new suit, and Stony romances Betty.