The study focuses on evidence of Cenozoic faulting in the epicentral area of the 1886 Charleston, South Carolina, earthquake and its connection with Mesozoic structure. The seismic data consist of several reflection profiles collected near Summerville, South Carolina, in the period 1975–1983. Reprocessing of the data reveals an extensive early Mesozoic extensional basin, approximately 20 km in width, between Summerville and Charleston. The basin is delineated by the geometry of reflections that image early Mesozoic volcanic and sedimentary rocks and by positive magnetic and gravity anomalies. Cenozoic compressional reactivation of Mesozoic extensional faults is imaged in the interior of the basin. The northwestern boundary of the basin is marked by a sharp gradient in the magnetic field. Folded Cretaceous and Tertiary Atlantic Coastal Plain sediments in association with diffractions and truncated reflections from the early Mesozoic section at four locations along this magnetic gradient indicate that the northwestern basin boundary is faulted. Instrumentally located earthquakes are clustered at the location of the faults imaged in the interior of the basin and in proximity to the northwestern basin margin. Modeling of magnetic and gravity data indicates that the upper crust beneath the seismically imaged structural basin is composed largely of mafic rocks to a depth of at least 4 km. We propose that the Charleston earthquake occurred due to compressional reactivation of a Mesozoic fault in a localized zone of intense early Mesozoic continental rifting.