We reconstructed paleoclimate patterns from oxygen and carbon isotope records from the fossil estuarine benthic foraminifera Elphidium and Mg/Ca ratios from the ostracode Loxoconcha from sediment cores from Chesapeake Bay to examine the Holocene evolution of North Atlantic Oscillation (NAO)-type climate variability. Precipitation-driven river discharge and regional temperature variability are the primary influences on Chesapeake Bay salinity and water temperature, respectively. We first calibrated modern δ¹⁸O_water to salinity and applied this relationship to calculate trends in paleosalinity from the δ¹⁸O_foram, correcting for changes in water temperature estimated from ostracode Mg/Ca ratios. The results indicate a much drier early Holocene in which mean paleosalinity was ∼28 ppt in the northern bay, falling ∼25% to ∼20 ppt during the late Holocene. Early Holocene Mg/Ca-derived temperatures varied in a relatively narrow range of 13° to 16°C with a mean temperature of 14.2°C and excursions above 16°C; the late Holocene was on average cooler (mean temperature of 12.8°C). In addition to the large contrast between early and late Holocene regional climate conditions, multidecadal (20–40 years) salinity and temperature variability is an inherent part of the region's climate during both the early and late Holocene, including the Medieval Warm Period and Little Ice Age. These patterns are similar to those observed during the twentieth century caused by NAO-related processes. Comparison of the midlatitude Chesapeake Bay salinity record with tropical climate records of Intertropical Convergence Zone fluctuations inferred from the Cariaco Basin titanium record suggests an anticorrelation between precipitation in the two regions at both millennial and centennial timescales.