The long-term monitoring of eight lakes near Dorset, Ontario, indicates that the water quality has changed significantly over the last 30 years. However, trends in the Dorset lakes may not be representative of changes in other south-central Ontario lakes, as the Dorset lakes are within a small area and span a limited gradient of lake and watershed characteristics. To determine the regional extent of water quality changes, we assessed the chemical changes in 36 diverse lakes that were first sampled between 1981 and 1990 and were resampled in 2004-2005. Similar to trends in the Dorset lakes, changes in the regional lakes included decreasing acidity, calcium, conductivity, metals, and phosphorus, and increasing dissolved organic carbon, nitrogen, sodium, and chloride. Water quality changes were driven by regional stressors, including acidic deposition, climate, and lakeshore residential development. However, stressor-induced responses differed among lakes. Increases in sodium and chloride were greater in developed lakes that were close to winter-maintained roads. Site-specific characteristics, such as lake and watershed morphometry, could not explain heterogeneous changes in the remaining water quality parameters. These results indicate that other factors play an important role in regulating individual lake response to regional stressors.