Isla Santa María at the active margin of south-central Chile is the result of earthquake-related uplift and deformation in the forearc since at least late Pleistocene time. Field mapping, dating of key depositional horizons, and analysis of seismic-reflection profiles reveal ongoing deformation in this sector of the Chilean forearc. The 30 km2 island is located ∼12 km above the interplate seismogenic zone and 75 km landward of the trench. It is situated near the southern termination of the Concepción earthquake rupture segment, where Charles Darwin measured 3 m of coseismic uplift during a M > 8 megathrust earthquake in 1835. Permanent postearthquake deformation from this earthquake and an earlier event in 1751 is registered by emerged, landward-tilted abrasion surfaces. Uplift at ∼2 m/k.y. and tilting at ∼0.025°/k.y. of the island have been fairly constant throughout the late Quaternary and have resulted in emergence of the island above sea level ∼31 k.y. ago. The island is composed of a late Pleistocene upper, tilted surface with two asymmetric tilt domains, and Holocene lowlands characterized by uplifted and tilted strandlines. Industry offshore seismic-reflection profiles covering an area of ∼1800 km2 and crustal seismicity reveal active reverse-fault cored anticlines surrounding Isla Santa María; the principal fault apparently roots in the plate-interface thrust. These reverse faults in the upper plate result from inversion of late Cretaceous to early Pliocene normal faults and rift structure of the Arauco forearc basin. Positive inversion of these inherited structures started between 3.6 and 2.5 Ma and resulted in continuous shortening rates of ∼0.8 mm/yr. The seismic-reflection profiles show that the asymmetric tilt domains and progressive syntectonic sedimentation are linked to the position of the island in the forelimbs of two converging anticlines, whereas their backlimbs have been removed by cliff retreat. The 2 m uplift contour of the 1835 earthquake is parallel to the strike of active faults and antiforms in the Arauco-Concepción region. The close relation among the asymmetric uplift and tilt of the island, modern deformation patterns, and reverse faults rooted in the plate interface suggests that slip on the plate interface thrust influences, localizes, and segments surface deformation during large interplate earthquakes. Furthermore, the link between positive inversion of pre-existing structures, uplift, and tilt patterns in the forearc emphasizes the importance of inherited structural fabrics in guiding plate-boundary deformation.