Makkah and central Red Sea regions have been re-evaluated from recent earthquake data analysis. Epicenters of recent seismic activity are concentrated in three local seismic zones. These are Ad Damm fault (NE), Nu’man–Makkah–Fatima (NW), and Jeddah-Red Sea (NW) seismic zones. Moreover, an extended seismic zone along the central part of Red Sea is observed. Most of these epicenters are distributed along tectonic faults, as indicated from the subsurface structure analysis of the aeromagnetic anomaly map. Some epicenters of small magnitudes are inaccurately located. The study indicates the existence of large active structural basin south of Makkah region, which traverse Ad Damm fault zone with the Red Sea transform faults. Slip vector analyses were carried out for 50 available earthquake focal mechanisms around Makkah region. In Nu’man, Makkah, and Fatima structural zones, the slip vectors generally trend NW and NNW. However, in the southern part at the Ad Dam structure zone, the slip vector trends NE–SW. These may result from the current complicated drifting motion of Arabian plate away from African plate combined with the opening of the Red Sea rift.