Analyses of sediment cores from Marcella Lake, a small, hydrologically closed lake in the semi-arid southwest Yukon, provides effective moisture information for the last ∼4500 years at century-scale resolution. Water chemistry and oxygen isotope analyses from lakes and precipitation in the region indicate that Marcella Lake is currently enriched in 18O by summer evaporation. Past lake water values are inferred from oxygen isotope analyses of sedimentary endogenic carbonate in the form of algal Charophyte stem encrustations. A record of the δ 18O composition of mean annual precipitation at Jellybean Lake, a nearby evaporation-insensitive system, provides data of simultaneous δ 18O variations related to decade-to-century scale shifts in Aleutian Low intensity/position. The difference between the two isotope records, Δδ, represents 18O-enrichment in Marcella Lake water caused by summer effective moisture conditions. Results indicate increased effective moisture between ∼3000 and 1200 cal BP and two marked shifts toward increased aridity at ∼1200 and between 300 and 200 cal BP. These prominent late Holocene changes in effective moisture occurred simultaneously with changes in Aleutian Low circulation patterns over the Gulf of Alaska indicated by Jellybean Lake. The reconstructed climate patterns are consistent with the topographically controlled climatic heterogeneity observed in the coastal mountains and interior valleys of the region today.