Stress changes produced by the 1906 San Francisco earthquake had a profound effect on the seismicity of the San Francisco Bay region (SFBR), dramatically reducing it in the twentieth century. Whether the SFBR is still within or has emerged from this seismic quiescence is an issue of debate with implications for earthquake mechanics and seismic hazards. Historically, the SFBR has not experienced one complete earthquake cycle (i.e., the accumulation of stress, its release primarily as coseismic slip during surface‐faulting earthquakes, its re‐accumulation in the interval following, and its subsequent rerelease). The historical record of earthquake occurrence in the SFBR appears to be complete at about M 5.5 back to 1850 (Bakun, 1999). For large events, the record may be complete back to 1776, which represents about half a cycle. Paleoseismic data provide a more complete view of the most recent pre‐1906 SFBR earthquake cycle, extending it back to about 1600. Using these, we have developed estimates of magnitude and seismic moment for alternative sequences of surface‐faulting paleoearthquakes occurring between 1600 and 1776 on the region’s major faults. From these we calculate seismic moment and moment release rates for different time intervals between 1600 and 2012. These show the variability in moment release and suggest that, in the SFBR regional plate boundary, stress can be released on a single fault in great earthquakes such as that in 1906 and in multiple ruptures distributed on the regional plate boundary fault system on a decadal time scale.