SUMMARY Subduction earthquakes show complex spatial and temporal rupture patterns, exhibiting events of varied sizes, which rupture distinct or overlapping fault segments. Elucidating first-order controlling conditions of rupture segmentation and return periods of large earthquakes is therefore critical for seismic and tsunami hazard estimations. The Chilean subduction zone frequently hosts several Mw > 8 earthquakes, with heterogeneous recurrence rates and locations. Here, we implement 3-D quasi-dynamic rate and state frictional models to investigate the role of plate interface geometry on the distribution of interseismic coupling and coseismic ruptures in Central Chile. First, we develop synthetic-parametric models that show how dip and strike variations may increase the probabilities to produce partial seismic barriers, which tend to avoid the production of large earthquake ruptures and modulate rupture lengths. Then, we simulate the subduction seismic cycle processes on Central Chile (25°S–38°S), imposing depth-dependent frictional properties on a realistic non-planar 3-D subduction interface geometry. Similar to results obtained for synthetic-parametric models, after 5000 yr of simulation, regions with abrupt dip or strike changes increase the probabilities of stopping coseismic propagation of simulated Mw 8.0–9.0 earthquakes. Our simulated earthquake sequences on the Central Chile subduction zone delimit rupture areas that match geometrical interface features and historical earthquakes, results that point to the crucial role of fault interface geometry on seismic cycle segmentation along strike.