Seismicity in the southeastern United States is relatively poorly characterized and thus not well understood. Structures and heterogeneities from multiple stages of Appalachian orogenesis, continental rifting, and magmatism as well as rivers and reservoirs may be influencing seismic activity in the region, but previous constraints are limited. The addition of seismic stations from the U.S. Transportable Array and the Southeastern Suture of the Appalachian Margin Experiment Array in 2012–2014 provide an opportunity to characterize seismicity in the central Georgia–South Carolina region. We develop a seismic catalog of events from March 2012 to May 2014 within or near the instrument array boundaries 30.1°–35.2°N, 80.9°– 85.7°W. Many of the events detected were industrial blasts, so multiple strategies were tested to discriminate between earthquakes and blasts based on event locations, timing, and spectral amplitude of the P and S arrivals. Based on this analysis, of the events in the catalog were classified as earthquakes. Most earthquakes southeast of the eastern Tennessee seismic zone are located in the Carolina terrane, particularly where the Carolina terrane intersects major rivers or reservoirs. One prominent region of seismicity along the Savannah River near Thurmond Lake corresponds with an rise in water levels in 2013. A temporal cluster of earthquakes in April 2013 was followed by increased levels of ambient seismicity preceding the nearby 4.1 earthquake in 2014. Focal mechanisms based on first‐motion polarities indicate strike‐slip to oblique‐thrust motion on structures trending approximately north–south or east–west, and a maximum horizontal stress orientation consistent with the regional trend of , implying that seismicity may reactivate more optimally oriented structures in the Carolina terrane that are oblique to the trend of the Appalachians. Seismicity in central Georgia appears to be controlled by a complex interaction between preexisting crustal structure and hydrologic variability.