The recent expansion of dense GPS networks over plate boundaries allows for remarkably precise mapping of interseismic coupling along active faults. The interseismic coupling coefficient is related to the ratio between slipping velocity on the fault during the interseismic period and the long-term plates velocity, but the interpretation of coupling in terms of mechanical behavior of the fault is still unclear. Here, we investigate the link between coupling and seismicity over the Chilean subduction zone that ruptured three times in the last 5 years with major earthquakes (Maule Mw 8.8 in 2010, Iquique Mw 8.1 in 2014 and Illapel Mw 8.4 in 2015). We combine recent GPS data acquired over the margin (38°–18°S) with older data to get the first nearly continuous picture of the interseismic coupling variations on the subduction interface. Here, we show that at least six low coupling zones (LCZ), areas where coupling is low relatively to the neighboring highly coupled segments can be identified. We also find that for the three most recent Mw > 8 events, co-seismic asperities correlate well with highly coupled segments, while LCZs behaved as barriers and stopped the ruptures. The relation between coupling and background seismicity in the interseismic period before the events is less clear. However, we note that swarm sequences are prone to occur in intermediate coupling areas at the transition between LCZ and neighboring segments, and that the background seismicity tends to concentrate on the downdip part of the seismogenic locked zone. Thus, highly coupled segments usually exhibit low background seismicity. In this overall context, the Metropolitan segment that partly ruptured during the 2015 Illapel earthquake appears as an outlier since both coupling and background seismicity were high before the rupture, raising the issue of the remaining seismic hazard in this very densely populated area.