Devastated by two earthquakes in historical times (1650 and 1950 CE), the Cusco Basin is now characterized by dense and chaotic urbanization that makes it even more vulnerable. Unfortunately, the large recurrence intervals of the local crustal earthquakes, the shortness of the historical record (∼500 yr) and the persistent lack of palaeoseismological studies hamper considerably the seismic hazard assessment. In such context, the outstanding archaeological heritage of the Cusco area turns out to be a relevant marker of past seismic activity. We carried out a systematic archaeoseismological survey in nine Inca sites close to Cusco and registered almost 3,000 Earthquake Archaeological Effects. Thanks to a semi-quantitative approach, we show a clear anisotropic seismic deformation on the Inca fine stonework, consistent at the regional scale. In Cusco, the architecture exhibits the impact of two different and strong ancient seismic events (M.M. intensity > VII). By combining these results with the analysis of historical photographs, our work supports, the occurrence of an unreported event during Inca times (∼1400–1533 CE). More broadly, by providing new data on the destructive potential of past earthquakes, this study urges us to conduct further research on the faults near Cusco.