Geneva Lake in Wisconsin, USA, is > 20,000 years old and contains a 30-m thick lacustrine sediment record of mid-continent North American climate and environmental change. Here we describe a sediment record from Geneva Lake spanning the past 14,500 years. From scanning X-ray fluorescence, organic C and N concentrations and isotopes, X-ray diffraction, magnetic susceptibility, and grain size of bulk sediments, we infer changes in sediment sources over time including: abrupt decline in inputs of remobilized loess ∼13,400 cal yr BP followed by a gradual transition to organic-rich marl deposition by ∼10,400 cal yr BP as the landscape stabilized following a period of permafrost thaw and vegetation development; deposition of a minerogenic unit at ∼8,200 cal yr BP that may record enhanced eolian activity during the widespread “8.2 ka event; ” and elevated zinc, lead, and arsenic from human activities following regional industrialization. Within the Holocene marl, we also use isotopic (δ18O and δ13C) and trace metal ratio (Sr/Ca and Mg/Ca) analyses of ostracode valves paired with concentrations and hydrogen isotopic composition (δ2H) of leaf wax n-alkanes to infer climate and hydrological change. Groundwater had a large but declining influence on lake water chemistry from 11,800 to 9,700 cal yr BP, precluding inferences of regional climate from our lacustrine proxies during this period. δ2H values of terrestrial n-C29 alkanes show little variability from 9,700 to present, indicating the average isotopic composition of local precipitation was relatively stable, reflecting stable condensation temperatures and source. In contrast, a gradual trend towards more δ18O- and δ2H-depleted lake water and lower lake water Sr/Ca from 9700 cal yr BP to present suggest decreasing evaporation of lake water and increasing precipitation amounts throughout the Holocene and resulting shorter lake water residence times. Lake water Mg/Ca variations over the past 9,700 years broadly parallel regional pollen-based reconstructions of summer temperatures. Neither Mg/Ca nor terrestrial leaf wax δ2H suggest long-term directional shifts in temperature at this site through the middle to late Holocene, as climate became wetter. It appears that precipitation isotopes did not track local temperatures on millennial timescales in this part of mid-continent North America through the Holocene, and instead may have covaried with changes in Northern Hemisphere latitudinal temperature gradients driven by large Arctic temperature changes.