Dybt inde i den bengalske jungle bor Kit Walker alias Fantomet. Sammen med hunden Devil og hesten Hero, holder Fantomet ro og orden i troperne. Det bliver der også brug for, da den magtsyge industrimagnat Xander Drax planlægger at overtage verdensherredømmet ved at finde og sammensætte tre magiske kranier.

A millionaire philanthropist collects the famous Crystal Skulls trying to tap into their ancient powers. It is up to a team lead by a college professor whose father disappeared searching for the 13th skull to save the world when the first 12 skulls are united and reek havoc on the earth without the control of the 13th skull.

One of archaeology's most compelling mysteries is that of the 13 crystal skulls. The crystal skulls have been some of the most powerful mystical symbols in human history. Several "perfect" crystal skulls have been found in parts of Mexico and Central and South America. Together, they form a mystery as enigmatic as the Great Pyramids and Stonehenge.