Ecological shifts, between a clear macrophyte-dominated state and a turbid state dominated by phytoplankton and high inorganic suspended solids, have been well described in shallow lake ecosystems. While few documented examples exist in rivers, models predict regime shifts, especially in regulated rivers with high water retention time. Here I quantified ecological shifts in a large, semi-regulated floodplain river during a transition from a turbid-to a clear-water state using water quality, aquatic vegetation and fisheries data from a rigorous, standardized long-term data set. My findings indicate that significant changes occurred in total suspended solids concentration, aquatic macrophyte abundance, native and non-native fish biomass, fish functional feeding guild patterns, fish habitat guild assemblages and fish spawning guild assemblage patterns over a nearly 20-year period in Navigation Pool 8 of the Upper Mississippi River. Transitions in physical and biological indicators were examined to identify mechanisms underlying the ecological shifts. Environmental variables driving fish assemblage changes were identified (total suspended solids and aquatic vegetation) and management-relevant thresholds are presented. Awareness of management thresholds is critical for resource managers to implement measures to prevent the river from moving to a degraded state characterized by high non-native fish abundance and low predatory fish species abundance.