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The Puebla‐Morelos (Mexico) 2017 earthquake nucleated ∼250 km inland from the trench within the Cocos oceanic plate mantle. Here, we argue that the Puebla‐Morelos (Mexico) 2017 earthquake resulted from changes in effective stress due to the reaction brucite + antigorite = olivine + H2O leading to the reactivation of pre‐existing seafloor faults. Fluid release (∼185 kg of H2O per m3 of subducted hydrated harzburgite) and volume increase (ΔVrsolid+fluid = ∼0.8%) likely occur along subducted seafloor‐inherited faults. The amount of H2O released, and magnitude of volume change depends on the degree of faults hydration; only highly hydrated (>40% of hydration) faults will stabilize brucite and experience this reaction at depth. The brucite + antigorite dehydration reaction may be key for intermediate seismicity worldwide. Plain Language Summary: The Puebla‐Morelos (central Mexico) Mw7.1 earthquake occurred in an uncommon locality in Mexico compared to most of the catastrophic earthquakes that have occurred in this part of the world—it nucleated ∼250 km inland, almost below Mexico City. In this paper, we explore the role of mineralogical changes occurring in the Cocos tectonic plate, which is currently descending below the North America plate. Our model tracked the changes in the minerals within the rocks and show that the earthquake might have been triggered by the physical changes associated with the mineral reaction: brucite + antigorite = olivine + H2O. We suggest that this mineral reaction primarily occurred along faults in the subducting oceanic floor along which the mantle lithosphere was hydrated prior to subduction. The brucite + antigorite dehydration reaction may be key for intermediate seismicity worldwide. Key Points: The dehydration of antigorite + brucite has a positive total volume change and leads to fluid‐induced fault reactivationWe hypothesize that fluid‐induced fault reactivation triggered the Puebla‐Morelos 2017 earthquakeThe antigorite + brucite reaction only happens in highly hydrated regions of the upper lithospheric mantle [ABSTRACT FROM AUTHOR]