Climate, vegetation cover, and management create finescale heterogeneity in unirrigated agricultural regions, with important but not well-quantified consequences for spatial and temporal variations in surface CO2, water, and heat fluxes. Eddy covariance fluxes were measured in seven agricultural fields—comprising winter wheat, pasture, and sorghum—in the U.S. Southern Great Plains (SGP) during the 2001–03 growing seasons. Land cover was the dominant source of variation in surface fluxes, with 50%–100% differences between fields planted in winter–spring versus fields planted in summer. Interannual variation was driven mainly by precipitation, which varied more than twofold between years. Peak aboveground biomass and growing season net ecosystem exchange (NEE) of CO2 increased in rough proportion to precipitation. Based on a partitioning of gross fluxes with a regression model, ecosystem respiration increased linearly with gross primary production, but with an offset that increased near the time of seed production. Because the regression model was designed for well-watered periods, it successfully retrieved NEE and ecosystem parameters during the peak growing season and identified periods of moisture limitation during the summer. In summary, the effects of crop type, land management, and water limitation on carbon, water, and energy fluxes were large. Capturing the controlling factors in landscape-scale models will be necessary to estimate the ecological feedbacks to climate and other environmental impacts associated with changing human needs for agricultural production of food, fiber, and energy.