The Irpinia region is one of the most seismically active areas of Italy due to ongoing, late-orogenic extension in the axial zone of the Apennines mountain belt. However, the 3D architecture and the nature of the faults that drive this extension are still uncertain, posing challenges to seismic hazard assessment. Here, we address these uncertainties by integrating a new catalog of high-resolution micro-seismicity (ML<3.5) complemented by earthquake focal mechanisms, with existing 3D seismic velocity models and geological data. We found that micro-seismicity is primarily taking place along a segmented, approximately 60 km long, deep-seated, Mesozoic normal fault that was inverted during the shortening stages of the Apennine orogeny and then extensionally reactivated during the Quaternary. These findings suggest that multiple events of reactivation of long-lived faults can weaken their strength, making them prone to co-seismic remobilization under newly-imposed strain fields in active mountain belts.