Side channels in large floodplain rivers serve a variety of important ecological roles, particularly in reaches where habitat conditions have been degraded or diminished. We developed hypotheses regarding side channel ecological structure whereby we expected species richness of young-of-year fishes to generally be higher in shallower, more physically heterogeneous side channels with lower velocities, with differences based on reproductive guild. We also hypothesized species richness of adult fishes to be higher in side channels with greater heterogeneity that could support diverse foraging resources and provide refugia during extreme flow conditions. To test these hypotheses, we used a 28-year fish community dataset from the Upper Mississippi and Illinois Rivers. Across six study reaches, we assessed metrics of side channel physical size, heterogeneity, and connectivity that were hypothesized to explain variance of fish community response, while accounting for site-level factors across 52 side channels using multilevel models. We then used these side channel-level characteristics in a K-means cluster analysis to classify 1126 side channels across 32 reaches of the river system. Our results indicated that the relative explanatory contributions of physical metrics varied by response variable, providing varying evidence in support of our hypotheses, and indicating that different forms of heterogeneity matter in different ways. Side channel-level factors were more explanatory of fish community responses in side channels of upstream reaches compared to downstream reaches and percent wet forest was the most explanatory side channel-level factor of fish community responses across all models. Our classification of side channels indicated strong spatial contrasts in the abundance and diversity of side channels across reaches. Scaling up to understand how the diversity and abundance of different types of side channels contributes to landscape-scale ecological functions and processes would be useful for establishing targets for reach-scale physical heterogeneity.