Interannual climate variability is expected to increase over the next century, but the extent to which hydroclimatic variability influences biogeochemical processes is unclear. To determine the effects of extreme weather on surface water chemistry, a 30-year record of surface water geochemistry for 84 lakes in the northeastern U.S. was combined with landscape data and watershed-specific weather data. With these data, responses in sulfate (SO₄ ²⁻) and dissolved organic carbon (DOC) concentrations were characterized during an extreme wet year and an extreme dry year across the region. Redundancy analysis was used to model lake chemical response to extreme weather as a function of watershed features. A response was observed in DOC and SO₄ ²⁻ concentration in response to extreme wet and dry years in lakes across the northeastern U.S. Acidification was observed during drought and brownification was observed during wet years. Lake chemical response was related to landscape characteristics in different ways depending on the type of extreme year. A linear relationship between wetland coverage and DOC and SO₄ ²⁻ deviations was observed during extreme wet years. The results presented here help to clarify the variability observed in long-term recovery from acidification and regional increases in DOC. Understanding the chemical response to weather variability is becoming increasingly important as temporal variation in precipitation is likely to intensify with continued atmospheric warming.