We compiled a novel microseismicity catalog for the Central Chile megathrust (29°–35°S), comprising 8,750 earthquakes between April 2014 and December 2018. These events describe a pattern of three trenchward open half-ellipses, consisting of a continuous, coast-parallel seismicity band at 30–45 km depth, and narrow elongated seismicity clusters that protrude to the shallow megathrust and separate largely aseismic regions along strike. To test whether these shapes could outline highly coupled regions (“asperities”) on the megathrust, we invert GPS displacement data for interplate locking. The best-fit locking model does not show good correspondence to seismicity, possibly due to lacking resolution. When we prescribe high locking inside the half-ellipses, however, we obtain models with similar data fits that are preferred according to the Bayesian Information Criterion (BIC). We thus propose that seismicity on the Central Chile megathrust may outline three adjacent highly coupled regions, two of them located between the rupture areas of the 2010 Maule and the 2015 Illapel earthquakes, a segment of the Chilean margin that may be in a late interseismic stage of the seismic cycle.