At Santorini, active normal faulting controls the emission of volcanic products. Such geometry has implication on seismic activity around the plumbing system during unrest. Static Coulomb stress changes induced by the 2011–2012 inflation within a preexisting NW-SE extensional regional stress field, compatible with fault geometry, increased by more than 0.5 MPa in an ellipsoid-shaped zone beneath the Minoan caldera where almost all earthquakes (96%) have occurred since beginning of unrest. Magmatic processes perturb the regional stress in the caldera where strike-slip rather than normal faulting along NE-SW striking planes are expected. The inflation may have also promoted more distant moderate earthquakes on neighboring faults as the M > 5 January 2012, south of Christiania. Santorini belongs to a set of en echelon NE-SW striking rifts (Milos, Nysiros) oblique to the Aegean arc that may have initiated in the Quaternary due to propagation of the North Anatolian fault into the Southern Aegean Sea.