The Pacific sector of Northwestern Patagonia (NWP, 40 degrees-44 degrees S) is key for examining the interaction between climate variability, explosive volcanism, and human influences on southern mid-latitude ecosystems. A limited number of studies in this region, however, have focused on aquatic ecosystem and hydrologic balance (HB) changes throughout the Holocene. Here we report a fossil diatom record from Lago Pichilaguna, a small closedbasin lake located in the lowlands of the Chilean Lake District, that reveals prominent changes in species composition and functional groups since 12.6 cal ka BP. We interpret positive HB between 12.6-11.4 cal ka BP and from 5.7 cal ka BP until recent that alternate with negative HB between 11.4-6.9 cal ka BP. We observe centennial-scale fluctuations since 5.7 cal ka BP that culminate with a negative HB phase over the past 270 years. Coherent responses in terrestrial and aquatic ecosystems recorded in the Lago Pichilaguna sediments underscore the influence of variations in the Southern Westerly Winds in NWP from multimillennial to centennial timescales since 12.6 cal ka BP. These inferences replicate the timing and direction of changes from previous studies at regional, pan-Patagonian, and zonal scales. The magnitude and rapidity of changes in diatom assemblages that started at 0.2 cal ka BP exceeds the ranges of local natural variability since 12.6 cal ka BP. This abrupt change is associated with a negative HB phase at centennial timescale, deposition of a tephra layer, and large-scale disturbance by Chilean/European settlers.