During the last decade, knowledge over episodic tremor and slip (ETS) events has increased dramatically owing to the widespread installation of GPS and seismic networks. The most puzzling observations are (i) the periodic nature of slow seismic events, (ii) their localization at intermediate depths (estimated 15-40 km), and (iii) the origin of the nonvolcanic fluids that are responsible for the tremor activity. We reconcile these observations using a first principles approach relying on physics, continuum mechanics, and chemistry of serpentinite in the megathrust interface. The approach reproduces the GPS sequences of 17 years of recording in Cascadia, North America, as well as over 10 years in the Hikurangi Trench of New Zealand. We show that strongly endothermic reactions, such as serpentinite dehydration, are required for ETS events. We report that in this tectonic setting, it is its chemical reaction kinetics, not the low friction, that marks serpentinite as a key mineral for stable, self-sustained oscillations. We find that the subduction zone instabilities are driven from the ductile realm rather than the brittle cover. Even when earthquakes in the cover perturb the oscillator, it relaxes to its fundamental mode. Such a transition from stable oscillations to chaos is witnessed in the ETS signal of NZ following the M6.8, 2007 seismic event, which triggered a secondary mode of oscillations lasting for a few years. We consequently suggest that the rich dynamics of ductile modes of failure may be used to decipher the chaotic time sequences underpinning seismic events. Key Points Serpentinite is key mineral in shear zones because of its dehydration kinetics Subduction zone instabilities are driven from the deep mantle The interaction between crust and mantle causes transition to chaos ©2014. American Geophysical Union. All Rights Reserved.