This study examines the response of a forearc to the increase in sediment flux to the trench caused by the onset of glacial denudation in the Patagonian Andes. We investigated shelf-coastal basins in south-central Chile, which generally comprise Eocene–early Miocene nearshore facies overlain by late Miocene–early Pliocene deep-water siltstones and by late Pliocene–Quaternary nearshore deposits. Seismic profiles and coastal exposures reveal Eocene–early Pliocene extension followed by ongoing late Pliocene compression evidenced from growth strata adjacent to seismically active reverse faults. The onset of major global cooling ca. 6 Ma triggered glacial denudation in the uplifted high Andes. Exhumed material transported along the steep and humid Andean western slope increased trench sedimentation rates and caused continuous accretion and subduction of terrigenous material. We interpret forearc basin inversion as a response to a decrease in slope and basal friction of the wedge caused by frontal accretion and subduction of water-rich material, respectively, in order to reach a critical taper. This process lifted the shelf ∼1.5 km during the middle Pliocene. The Juan Fernández Ridge and Chile Rise confined >2 km trench fill between 45 and 34°S, limiting accretion and basin inversion. Glacial age trench fill and the steady decrease in plate convergence rate shifted this segment of the margin from erosive to accretionary during the Pliocene.