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In this study, we investigate a little-known earthquake that struck Cascia and its environs (Central Italian Apennines) in 1599, causing 50 casualties and the destruction and abandonment of several settlements. As in current seismic catalogues the characterization of this event is based on the anonymous account of a single source, we conducted research using public and private archives and libraries that allow recovering many unpublished contemporary accounts of the earthquake. This information permitted a more detailed evaluation of the macroseismic effects and a doubling of the number of intensity datapoints, resulting in a more robust earthquake epicentral parameters. Next, we conducted a geological field survey within the newly defined mesoseismic area aimed at finding possible evidence of active tectonics, likely faults with indications of recent movements and with an attitude fitting both the 1599 highest intensity distribution and the regional stress field. We found evidence for Holocene surface faulting along the Cascia and Mount Alvagnano faults that we consider responsible for the 1599 earthquake, and possibly also for a twin event in 1979 and the much stronger Norcia earthquake in 1703. • New archive findings allowed doubling the 1599 earthquake datapoints. • Mt. Alvagnano-Cascia faults ruptured at surface in Holocene-historic time. • Three M ≥ 6 earthquakes in the past 400 years were sourced by Mt. Alvagnano-Cascia faults. • Norcia fault system segments ruptured alone or together sourcing 6 ≤ Mw ≤ 6.9 earthquakes. [ABSTRACT FROM AUTHOR]