This study presents the results of a geomorphological and paleoseismological investigation on the Angelochori normal fault. This fault controls the southern boundary of the Anthemountas basin and constitutes the western segment of the Anthemountas extensional detachment fault (AEDF), a ∼48 km-long, E-W-trending, north-dipping low-angle normal fault in Central Macedonia, Greece. To assess the relative tectonic activity of the Angelochori fault and to determine the number, timing, and displacement of surface-faulting earthquakes, we conducted detailed field mapping and paleoseismological investigations. Our approach involved utilizing geomorphic indices, analyzing stratigraphic and structural relations, considering luminescence ages, and employing OxCal modeling techniques. The acquired data reveal, for the first time, the Middle-Late Holocene activity of the Anghelochori fault, providing constraints on the age of three strong (M > 6) surface-rupturing earthquakes over the last ∼7.7 ka. The youngest of these events aligns with the historical earthquake of the Anthemountas basin in 1677 CE. The observed minimum displacement per event ranges from 0.48 m to 0.65 m, consistent with a fault length estimated at about 24–28 km, suggesting an earthquake magnitude on the order of 6.6. The cumulative slip rate over the recorded period averages 0.21 ± 0.02 mm/a, with an average open recurrence interval of 2.6 ± 0.2 ka. Nonetheless, the displacement pattern displays alternating intervals of rapid slip at 0.60 ± 0.16 mm/a and slower slip at 0.08 ± 0.01 mm/a. Classified as Class 1, the Angelochori fault signifies an active tectonic structure posing a significant seismic hazard for the Thessaloniki metropolitan area.