Abstract Dehydration reactions in subducted slabs have long been correlated with embrittlement and intermediate‐depth earthquakes. However, the physical process of dehydration embrittlement remains unclear due to the complex and poorly constrained interactions between reaction progress, fluid pressure evolution, and deformation. Here we aim to quantify these interactions during antigorite dehydration with 2D hydro‐mechanical‐chemical numerical modeling and explore whether the reaction causes stress perturbations potentially leading to earthquakes. Negative total volume change during the reaction acts toward the relaxation of fluid overpressures, decreasing the chance of embrittlement. The reaction zone is the least likely to fracture due to reaction‐induced weakening and the locally larger increase of total pressure compared to fluid pressure. However, weakening also generates fluid overpressure zones and may induce strain localization/runaway processes potentially leading to brittle failure. Our results also imply that antigorite dehydration could be both the cause and effect of fast deformation in subducted slabs.