The world's largest inland delta, located on the Okavango River in Botswana, faces major changes in the annual flooding size and duration due to climatic shifts and increased water use. We examined several parameters of a seasonal floodplain in the Okavango Delta during two years of contrasting flooding size. The small flood (2003) was characterized by high concentrations of total nutrients (2.5 mg N and 1 mg P L−1), high primary production (0.8 mg C m−3 d−1), and zooplankton biomass (30 mg DW L−1). Methane production and consumption was considerable and stable isotope analysis suggested that methane oxidation provided a significant input of C to the aquatic food web. The large flood (2004) was characterized by lower volume-specific productivity, lower concentrations of nutrients (1 mg N and 10 μg P L−1), lower primary production (45 mg C m−3 d−1), reduced zooplankton biomass (10 μg DW L−1), and low methane production. The density of fish (CPUE) was significantly higher for the large flood compared to the small one. The findings point to the overall importance of flooding size on primary and secondary production, as well as basic food web properties in the delta. Low floods mean higher volume-specific production at the base of the food web. Seasons of large and long lasting floods cause improved circulation and enhanced reproductive success for fish.