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ABSTRACT Phytoplankton form the base of large river food webs, but there are limited studies on the nature and drivers of communities over longer time scales. Further, climate change is projected to favour taxa associated with harmful algal blooms, but our knowledge of the timing, locations and drivers of cyanobacteria in rivers lags that of lakes and marine environments. We used a summer phytoplankton community dataset collected from 2010 to 2020 across the main channel, side channel and backwater areas in the La Grange reach of the Illinois River to assess: (1) How much do summer phytoplankton communities across diverse aquatic areas within a large river vary from year to year? (2) What environmental conditions are associated with that variation? and (3) Do cyanobacteria respond differently than the full phytoplankton community? We found greater differences in phytoplankton communities across years than among aquatic areas. Further, we showed that annual variation in phytoplankton communities was synchronous among taxa in the same aquatic area, rather than specific to each taxonomic group or taxa‐area combination. After accounting for this spatial variation in annual dynamics, phytoplankton reflected river conditions across seasons, responding positively to summer total phosphorus and invasive carp abundance and negatively to winter discharge and spring silica to nitrogen ratio. Annual variation in cyanobacteria was similarly distinct among main channel, side channel and backwater areas but was best explained by the ratio of summer air temperature to discharge, representing conditions that favoured growth over transport. These results show that annual variation in summer phytoplankton and cyanobacterial communities reflected the spatial diversity of the river landscape and responded to conditions that occurred across seasons. Further, in this highly modified river basin, we showed that a mix of anthropogenic pressures including eutrophication, invasive species and potential changes to winter and spring conditions affected the phytoplankton communities present in the summer. Thus, when evaluating long‐term change and the potential for harmful algal blooms in rivers, it is important to consider the spatial diversity of phytoplankton communities, how their sensitivity to environmental change may vary across the river landscape, and the suite of human modifications acting on those communities.