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Slab window formation provides a mechanism for the atypical exchange of mass and energy between the regions beneath (sub-slab) and above (supra-slab) a subducting plate, and its diagnosis is essential for our understanding of the thermal and compositional evolution of the lithosphere. We combine whole-rock geochemical data with new detrital zircon petrochronology to show a dramatic compositional change in the Central American arc in Panama at ca. 25 Ma. This change is characterized by (1) coupled enrichment in high field strength elements and fluid-immobile elements, (2) a local shift from hydrous to hot and dry magmatism, and (3) enhanced contribution of lower crustal materials. Such features indicate a reduction in the subduction signal and increased input of magma from primitive mantle sources, accompanied by local high heat flow. We relate these changes to the combined effects of collision-driven rupture of the Central American arc and the formation of a slab window resulting from the subduction of the Cocos-Nazca ridge after the breakup of the Farallon plate.