Terrestrial glacial records from the Patagonian Andes and New Zealand Alps document quasi-synchronous Southern Hemisphere–wide glacier advances during the late Quaternary. However, these records are inherently incomplete. Here, we provide a continuous marine record of western–central Patagonian ice sheet (PIS) extent over a complete glacial–interglacial cycle back into the penultimate glacial (~140 ka). Sediment core MR16-09 PC03, located at 46°S and ~150 km offshore Chile, received high terrestrial sediment and meltwater input when the central PIS extended westward. We use biomarkers, foraminiferal oxygen isotopes, and major elemental data to reconstruct terrestrial sediment and freshwater input related to PIS variations. Our sediment record documents three intervals of general PIS marginal fluctuations, during Marine Isotope Stage (MIS) 6 (140 to 135 ka), MIS 4 (~70 to 60 ka), and late MIS 3 to MIS 2 (~40 to 18 ka). These higher terrigenous input intervals occurred during sea-level low stands, when the western PIS covered most of the Chilean fjords, which today retain glaciofluvial sediments. During these intervals, high-amplitude phases of enhanced sediment supply occur at millennial timescales, reflecting increased ice discharge most likely due to a growing PIS. We assign the late MIS 3 to MIS 2 phases and, by inference, older advances to Antarctic cold stages. We conclude that the increased sediment/meltwater release during Southern Hemisphere millennial-scale cold phases was likely related to higher precipitation caused by enhanced westerly winds at the northwestern margin of the PIS. Our records complement terrestrial archives and provide evidence for PIS climate sensitivity.