We present here a simplified approach to quantifying regional seismic risk. The seismic risk for a given region can be inferred in terms of average annual loss (AAL) that represents long-term value of earthquake losses in any one year caused from a long-term seismic hazard. The AAL are commonly measured in the form of earthquake shaking-induced deaths, direct economic impacts or indirect losses caused due to loss of functionality. In the context of South American subcontinent, the analysis makes use of readily available public data on seismicity, population exposure, and the hazard and vulnerability models for the region. The seismic hazard model was derived using available seismic catalogs, fault databases, and the hazard methodologies that are analogous to the U.S. Geological Survey’s national seismic hazard mapping process. The Prompt Assessment of Global Earthquakes for Response (PAGER) system’s direct empirical vulnerability functions in terms of fatality and economic impact were used for performing exposure and risk analyses. The broad findings presented and the risk maps produced herein are preliminary, yet they do offer important insights into the underlying zones of high and low seismic risks in the South American subcontinent. A more detailed analysis of risk may be warranted by engaging local experts, especially in some of the high risk zones identified through the present investigation.