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What controls subduction megathrust seismogenesis downdip of the mantle wedge corner (MWC)? We propose that, in the region of the 2010 Mw= 8.8 Maule, Chile, earthquake, serpentine minerals derived from the base of the hydrated mantle wedge exert a dominant control. Based on modeling, we predict that the megathrust fault zone near the MWC contains abundant lizardite/chrysotile‐rich serpentinite that transforms to antigorite‐rich serpentinite at greater depths. From the MWC at 32–40 km depth to at least 55 km, the predominantly velocity‐strengthening megathrust accommodated dynamic propagation of the 2010 rupture but with small slip and negative stress drop. The downdip distribution of interplate aftershocks exhibits a gap around the MWC that can be explained by the velocity‐strengthening behavior of lizardite/chrysotile. Interspersed velocity‐weakening and dynamic weakening antigorite‐rich patches farther downdip may be responsible for increased abundance of aftershocks and possibly for some of the high‐frequency energy radiation during the 2010 rupture. A subduction megathrust rupture may extend from the trench to beneath populated coastal area. To understand what controls the megathrust seismogenic behavior of its deeper part, we conduct a case study of the 2010 magnitude 8.8 Maule, Chile, earthquake and its aftershocks. With numerical thermal modeling, we find that the deep seisomogenic behavior may be controlled by serpentine materials derived from the base of the overlying hydrated mantle wedge. The deep part of the megathrust ruptured “passively” against increasing resistance (negative stress drop). Lower‐temperature serpentines lizardite and chrysotile that are known to facilitate aseismic slip may be responsible for an observed gap in aftershock distribution in the downdip direction. Higher‐temperature serpentine antigorite that is known to facilitate seismic slip may be responsible for increased aftershocks farther downdip and possibly radiation of high‐frequency energy during the 2010 Maule earthquake. Seismogenic behavior of subduction megathrust may be affected by materials derived from the base of the serpentinized forearc mantle wedgeThermopetrologic modeling suggests abundance of lizardite and chrysotile around the mantle wedge corner but antigorite farther downdipSerpentine frictional behavior may explain distributions of stress drop and seismic energy radiation in 2010 rupture and aftershocks