On 1 April 2014, Northern Chile was struck by a magnitude 8.1 earthquake following a protracted series of foreshocks. The Integrated Plate Boundary Observatory Chile monitored the entire sequence of events, providing unprecedented resolution of the build-up to the main event and its rupture evolution. Here we show that the Iquique earthquake broke a central fraction of the so-called northern Chile seismic gap, the last major segment of the South American plate boundary that had not ruptured in the past century(1,2). Since July 2013 three seismic clusters, each lasting a few weeks, hit this part of the plate boundary with earthquakes of increasing peak magnitudes. Starting with the second cluster, geodetic observations show surface displacements that can be associated with slip on the plate interface. These seismic clusters and their slip transients occupied a part of the plate interface that was transitional between a fully locked and a creeping portion. Leading up to this earthquake, the b value of the foreshocks gradually decreased during the years before the earthquake, reversing its trend a few days before the Iquique earthquake. The mainshock finally nucleated at the northern end of the foreshock area, which skirted a locked patch, and ruptured mainly downdip towards higher locking. Peak slip was attained immediately downdip of the foreshock region and at the margin of the locked patch. We conclude that gradual weakening of the central part of the seismic gap accentuated by the foreshock activity in a zone of intermediate seismic coupling was instrumental in causing final failure, distinguishing the Iquique earthquake from most great earthquakes. Finally, only one-third of the gap was broken and the remaining locked segments nowpose a significant, increased seismic hazard with the potential to host an earthquake with a magnitude of > 8.5.