The Younger Dryas (YD) impact hypothesis posits that fragments of a large, disintegrating asteroid/comet struck North America, South America, Europe, and western Asia ~12,800 years ago. Multiple airbursts/impacts produced the YD boundary layer (YDB), depositing peak concentrations of platinum, high-temperature spherules, meltglass, and nanodiamonds, forming an isochronous datum at >50 sites across ~50 million km² of Earth’s surface. This proposed event triggered extensive biomass burning, brief impact winter, YD climate change, and contributed to extinctions of late Pleistocene megafauna. In the most extensive investigation south of the equator, we report on a ~12,800-year-old sequence at Pilauco, Chile (~40°S), that exhibits peak YD boundary concentrations of platinum, gold, high-temperature iron- and chromium-rich spherules, and native iron particles rarely found in nature. A major peak in charcoal abundance marks an intense biomass-burning episode, synchronous with dramatic changes in vegetation, including a high-disturbance regime, seasonality in precipitation, and warmer conditions. This is anti-phased with northern-hemispheric cooling at the YD onset, whose rapidity suggests atmospheric linkage. The sudden disappearance of megafaunal remains and dung fungi in the YDB layer at Pilauco correlates with megafaunal extinctions across the Americas. The Pilauco record appears consistent with YDB impact evidence found at sites on four continents.