Simulated global changes, including warming, increased precipitation, and nitrogen deposition, alone and in concert, increased net primary production (NPP) in the third year of ecosystem-scale manipulations in a California annual grassland. Elevated carbon dioxide also increased NPP, but only as a single-factor treatment. Across all multifactor manipulations, elevated carbon dioxide suppressed root allocation, decreasing the positive effects of increased temperature, precipitation, and nitrogen deposition on NPP. The NPP responses to interacting global changes differed greatly from simple combinations of single-factor responses. These findings indicate the importance of a multifactor experimental approach to understanding ecosystem responses to global change.