Salinity oscillations caused by multidecadal climatic variability had major impacts on the Chesapeake Bay estuarine ecosystem during the past 1000 yr. Microfossils from sediments dated by radiometry (14C, 137Cs, 210Pb) and pollen stratigraphy indicate that salinity in mesohaline regions oscillated 10–15 ppt during periods of extreme drought (low fresh-water discharge) and wet climate (high discharge). During the past 500 yr, 14 wet-dry cycles occurred, including sixteenth and early seventeenth century megadroughts that exceeded twentieth century droughts in their severity. These droughts correspond to extremely dry climate also recorded in North American tree-ring records and by early colonists. Wet periods occurred every ∼60–70 yr, began abruptly, lasted <20 yr, and had mean annual rainfall ∼25%–30% and fresh-water discharge ∼40%–50% greater than during droughts. A shift toward wetter regional climate occurred in the early nineteenth century, lowering salinity and compounding the effects of agricultural land clearance on bay ecosystems.