We analyzed net CO2 exchange data from 13 flux tower sites with 27 site-years of measurements over maize and wheat fields across midcontinent North America. A numerically robust “light-soil temperature-VPD”-based method was used to partition the data into photosynthetic assimilation and ecosystem respiration components. Year-round ecosystem-scale ecophysiological parameters of apparent quantum yield, photosynthetic capacity, convexity of the light response, respiration rate parameters, ecological light-use efficiency, and the curvature of the VPD-response of photosynthesis for maize and wheat crops were numerically identified and interpolated/extrapolated. This allowed us to gap-fill CO2 exchange components and calculate annual totals and budgets. VPD-limitation of photosynthesis was systematically observed in grain crops of the region (occurring from 20 to 120 days during the growing season, depending on site and year), determined by the VPD regime and the numerical value of the curvature parameter of the photosynthesis-VPD-response, σVPD. In 78% of the 27 site-years of observations, annual gross photosynthesis in these crops significantly exceeded ecosystem respiration, resulting in a net ecosystem production of up to 2100 g CO2 m−2 year−1. The measurement-based photosynthesis, respiration, and net ecosystem production data, as well as the estimates of the ecophysiological parameters, provide an empirical basis for parameterization and validation of mechanistic models of grain crop production in this economically and ecologically important region of North America.