Based on an analysis of sediment cores from Baptiste Lake (Alberta, Canada), we quantified century-scale trends in cyanobacteria and cyanotoxins, and identified possible drivers of toxigenic cyanobacteria. We measured concentrations of microcystins and pigments preserved in the sediment as proxies of toxigenic cyanobacteria and phytoplankton communities, respectively, while fossil diatom assemblages were used to infer past nutrient concentrations. Microcystins were detected in older sediments (ca. 1800s), pre-dating any significant alteration to the watershed. This demonstrates that toxigenic cyanobacteria may not be a recent phenomenon in eutrophic ecosystems. The dominant variants of microcystin throughout the sediment core were microcystin-LA and microcystin-LR. Other congeners including -LY, -7dmLR, -WR, -LF, -YR, and -LW (-RR was not detected) were mainly found in the upper layers of sediment (post 1980s). Starting in the 1990s, concentrations of microcystins both in the water column and in the sediment record increased in parallel. Total sediment microcystins were strongly correlated with historical nitrogen and phosphorus concentrations inferred from diatom assemblages (r=0.80-0.81, p<0.001, n=22); both nutrients increased over the past two decades coincident with the intensification of agriculture. Microcystins also tracked the rise in cyanobacterial pigments present throughout the core. In contrast, we found no relationship between climate-related variables and sediment microcystin concentrations, although such relationships were detected over the monitoring record with respect to water column concentrations. Overall, the rise in sediment microcystins was much greater than the rise in sediment cyanobacteria and diatom inferred nutrient concentrations. Furthermore, we demonstrate that the reconstruction of the microcystin sediment record can provide important insight for the development of realistic lake management goals. Applying this analytical approach to different lakes and regions of the world, where both natural and anthropogenic gradients vary, has the potential to markedly improve our understanding of long-term drivers of cyanotoxin production.