The global climate is changing and much of this is attributed to the greenhouse effect, which has been exacerbated by increased anthropogenic releases of greenhouse gases (GHGs). However, important GHGs, carbon dioxide (CO2), nitrous oxide (N2O), and methane (CH4), are produced naturally in the soil during the metabolism of many soil microbial and plant communities. The generation rate of GHGs depends on many factors, including soil community composition, nutrient availability, temperature, and soil moisture. Predicted climate variability is expected to alter temperature and rainfall patterns, which can impact the factors regulating natural generation of GHGs. With changing fluxes of GHGs, the natural feedback loops between GHG generation and climate may change. Increased emissions from natural sources would exacerbate climate change, whereas decreased emissions may mitigate its impacts. Floodplains may be particularly susceptible to climate change, as their biogeochemical processing is driven by hydrology. For this study, ten mesocosms were installed on the floodplain of Stroubles Creek in southwest Virginia. A flood event was simulated in half of these mesocosms in both early spring and mid-summer, which represent extremes in soil moisture and primary productivity on the floodplain. Headspace gases were monitored for CO, N2O, and CH4. Efflux of CO2 and N2O was higher in summer than spring, and also increased following wetting events. Methane production was greater in the spring, with no detectable change with wetting. Increases in summer rainfall events could increase the release of important GHGs to the atmosphere, potentially at levels significant to climate change.