Floodplain connectivity is important to aquatic organisms in large rivers. Anthropogenic alterations regulating the Missouri River have limited connectivity and negatively affected native fauna. Determining the biological response to rare inundation events may be important when considering potential restoration options on a regulated river; thus, we assessed benthic invertebrate and zooplankton communities at three floodplain sites during a historic Missouri River high-water event. Chironomid larvae dominated during most sampling trips and densities were often highest during initial sampling trips with lower densities as high water persisted. Similar trends were evident for rotifer, cladoceran, and copepod densities. Nonmetric multidimensional scaling also showed relatively high dissimilarity of densities between early and late sampling trips for benthic invertebrate and zooplankton communities. As such, short-term inundation may be more beneficial to Missouri River benthic invertebrate (mainly chironomid larvae) and zooplankton production than more prolonged inundation lasting a month or more. Furthermore, restoration projects may be designed at elevations allowing more short-term inundation, which would likely benefit native fishes with additional spawning, nursery, and foraging habitat. Levee setbacks may be an effective restoration option for increasing the amount of habitat available for short-term inundation while potentially providing socioeconomic, flood-risk reduction benefits by enhancing flow conveyance.