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Evaluation of large lake response to centennial changes in land use and climate can be complicated by high spatial and hydrological complexity within their catchments, particularly in regions of low relief. Furthermore, large lakes can exhibit abrupt changes in structure and function that obscure causes of eutrophication.We provide the first quantification of historical trends in lake production, cyanobacterial abundance, sediment geochemistry and diatom composition since c. 1800 in Lake Manitoba, the 29th largest lake in the world, and compared them to Lake Winnipeg, a morphologically similar, adjacent basin with a 10‐fold larger catchment and an abrupt increase in production around 1990.Before 1900, Lake Manitoba was mesotrophic, with low sedimentary concentrations of carbon, phosphorus, nitrogen, cyanobacteria and algal pigments, as well as assemblages of low‐light‐adapted benthic diatoms. Analysis of pigment time‐series with hierarchical generalised additive models revealed that Lake Manitoba eutrophied during 1900–1930 as a consequence of the development of intensive agriculture within its local catchment, but thereafter exhibited stable cyanobacterial densities with limited expansion of N2‐fixing cyanobacteria despite persistent eutrophication.Lake Manitoba did not undergo an abrupt change as seen in Lake Winnipeg.These findings suggest that catchment size had little influence on water quality degradation and that nutrient influx from proximal agricultural sources was sufficient to initially degrade these large prairie lakes. The abrupt change in Lake Winnipeg around 1990 required additional intensification of local land use that did not occur in the Lake Manitoba catchment. [ABSTRACT FROM AUTHOR]