The San Gregorio fault is the principal active fault west of the San Andreas fault in central coastal California, yet it remains the largest known fault in the region whose seismogenic potential is not known. In this study, we integrate traditional paleoseismic and archaeologic investigations to define the location, style, and timing of slip events on the northern San Gregorio fault at a site near Seal Cove in Moss Beach, California. The on-land portion of the San Gregorio fault at Seal Cove is a late-Holocene active dextral slip fault. Trench excavations revealed a broad zone of faulting, at least 22 m wide, consisting of five Holocene-active strands. These include a single mid-Holocene east-vergent reverse fault and four late-Holocene near-vertical strike-slip faults. The most recent event occurred after the deposition of a native Californian cooking hearth dated A.D. 1270 to A.D. 1400, but prior to the arrival of Spanish missionaries ca. 1775. The penultimate event at the site is less well constrained but appears to have occurred between A.D. 620 and A.D. 1400. The penultimate event was associated with horizontal displacement on the order of 3 m, based on reconstruction of a thrust wedge within the fault zone. The geometry of midden deposits shows a 5 (−2, +6) m deflection along the projection of faults associated with the most recent event (MRE). All or part of this deflection may be associated with the MRE. These displacements are consistent with Mw 7 to 7¼ earthquakes and show that the San Gregorio fault is an active seismogenic source that should be considered in seismic hazard assessments in the San Francisco Bay area.