Although the cyanobacterial toxin microcystin has been detected in Canadian fresh waters, little is known about its prevalence on a national scale. Here, we report for the first time on microcystin in 246 water bodies across Canada based on 3474 analyses. Over the last 10 years, microcystins were detected in every province, often exceeding maximum guidelines for potable and recreational water quality. Microcystins were virtually absent from unproductive systems and were increasingly common in nutrient-rich waters. The probable risk of microcystin concentrations exceeding water quality guidelines was greatest when the ratio of nitrogen (N) to phosphorus (P) was low and rapidly decreased at higher N:P ratios. Maximum concentrations of microcystins occurred in hypereutrophic lakes at mass ratios of N:P below 23. Our models may prove to be useful screening tools for identifying potentially toxic “hotspots” or “hot times” of unacceptable microcystin levels. A future scientific challenge will be to determine whether there is any causal link between N:P ratios and microcystin concentrations, as this may have important implications for the management of eutrophied lakes and reservoirs.