Incidence of elevated harmful algal blooms and concentrations of microcystin are increasing globally as a result of human-mediated changes in land use and climate. However, few studies document changes in the seasonal and interannual concentrations of microcystin in lakes. Here, we modeled 11 yr of biweekly microcystin data from six lakes to characterize the seasonal patterns in microcystin concentration and to ascertain if there were pronounced changes in the patterns of potential human exposure to microcystin in lakes of central North America. Bayesian time series analysis with generalized additive models found evidence for a regional increase in microcystin maxima and duration but recorded high variation among lakes. During the past decade, warmer temperatures, but not nutrient levels, led to a marked increase in the number of days when concentrations exceeded drinking and recreational water thresholds set by the World Health Organization and United States Environmental Protection Agency.