Multi-decadal to centennial-scale shifts in effective moisture over the past two millennia are inferred from sedimentary records from six lakes spanning a ~250 km region in northwest Ontario. This is the first regional application of a technique developed to reconstruct drought from drainage lakes (open lakes with surface outlets). This regional network of proxy drought records is based on individual within-lake calibration models developed using diatom assemblages collected from surface sediments across a water-depth gradient. Analysis of diatom assemblages from sediment cores collected close to the near-shore ecological boundary between benthic and planktonic diatom taxa indicated this boundary shifted over time in all lakes. These shifts are largely dependent on climate-driven influences, and can provide a sensitive record of past drought. Our lake-sediment records indicate two periods of synchronous signals, suggesting a common large-scale climate forcing. The first is a period of prolonged aridity during the Medieval Climate Anomaly (MCA, c. 900-1400 CE). Documentation of aridity across this region expands the known spatial extent of the MCA megadrought into a region that historically has not experienced extreme droughts such as those in central and western north America. The second synchronous period is the recent signal of the past ~100 years, which indicates a change to higher effective moisture that may be related to anthropogenic forcing on climate. This approach has the potential to fill regional gaps, where many previous paleo-lake depth methods (based on deeper centrally located cores) were relatively insensitive. By filling regional gaps, a better understanding of past spatial patterns in drought can be used to assess the sensitivity and realism of climate model projections of future climate change. This type of data is especially important for validating high spatial resolution, regional climate models.