Floodplain rivers have been conceptualized as patchwork mosaics of hydrogeomorphic zones that differ in hydrological, physiochemical, and ecological conditions. However, few investigators have empirically examined the extent to which basic ecological properties of large rivers, such as nutrient concentrations, are patchily distributed or the relationship between such distributions and water-mediated connectivity. We used global and local measures of spatial autocorrelation in 5 reaches of the Upper Mississippi River from 1994–2008 in spring (higher discharge) and summer (lower discharge) to examine distributions of total N (TN), total P (TP), and TN∶TP for evidence of patchiness. TN was distributed as discrete patches regardless of season, but the patches of TP and TN∶TP were more distinct during summer low-flow than spring high-flow conditions. The occurrence of patches of high TN, low TP, and high TN∶TP was highly predictable, generally occurring in backwater, low-velocity (0.1 m/s) environments. Patches of low TN, high TP, and low TN∶TP were less common and less predictable, but were more likely to occur in channels with high current velocities (>0.1 m/s) or in impounded areas with low current velocity, but adjacent to channel environments. These patch distributions are consistent with our current understanding of dominant mechanisms of riverine nutrient cycling and were generally consistent across 5 river reaches that spanned nearly the entire length of a large floodplain river. Watershed characteristics ultimately determine nutrient inputs to river systems, but our results support the idea that local geomorphic and hydraulic conditions influence spatial patterns of nutrient delivery and biochemical transformation and create a patchwork mosaic of nutrient distributions within large floodplain rivers.