Abstract Seismic velocity models were compared with coseismic slip distributions for two megathrust earthquakes that occurred along the South American subduction zone. By analyzing the distribution of Vp/Vs ratios, we found that seismic anomalies with values higher or lower than the average coincide with the boundaries of the earthquake ruptures. In contrast, the regions characterized by intermediate Vp/Vs values may represent a mechanical “sweet spot” where the physical properties create favorable conditions for sustained rupture propagation. Our methodology, which combines the Vp/Vs distribution and the analysis of coseismic slip models, could reveal the rupture‐prone regions and the likely magnitude of potential earthquakes, providing relevant information for seismic hazard assessment.