Great subduction earthquakes rupture similar regions of the megathrust during successive events separated by centuries. Mapping these regions (asperities) and their boundaries (barriers) is important for our understanding of processes controlling megathrust segmentation and for seismic hazard assessment. We present a formal seismic segmentation model of the Chile Margin derived from a multivariate analysis of gravity anomalies, basal friction from critical taper and interplate locking from GPS velocities. These proxies integrate over timescales of 10 to 10 years and we analyze their combined spatial covariance using Principal Component Analysis (PCA), from which the Empirical Orthogonal Functions (EOFs) and Principal Components (PCs) are extracted. We find that the 1 and 1+2 PCA modes explain 44% and 67% of the total variance, respectively, suggesting a high degree of spatial correlation. Comparing our results with rupture areas of earthquakes and using the rate-and-state friction theory, we infer that trench-perpendicular PCs reflect the limits of the velocity-weakening (VW) seismogenic zone. Polarity changes in along-trench EOFs (mostly for gravity) are related to changes between unstable and conditionally-stable frictional regimes inside the VW zone and we used them to define the boundaries of 17 unitary segments. These segments correlate with first-order tectonic features of the Andes at >10-km scales as well as with zones of multi-segment ruptures at 10-km scale. We analyze the combined influence of subducting and upper-plate geologic features on the nature of persistent seismic barriers. Our results have implications for understanding seismotectonic processes along the Andean margin and elsewhere