Diazotrophic marine cyanobacteria in the genus Trichodesmium contribute a large fraction of the new nitrogen entering the oligotrophic oceans, but little is known about how they respond to shifts in global change variables such as carbon dioxide (CO₂) and temperature. We compared Trichodesmium dinitrogen (N₂) and CO₂ fixation rates during steady-state growth under past, current, and future CO₂ scenarios, and at two relevant temperatures. At projected CO₂ levels of year 2100 (76 Pa, 750 ppm), N₂ fixation rates of Pacific and Atlantic isolates increased 35–100%, and CO₂ fixation rates increased 15-128% relative to present day CO₂ conditions (39 Pa, 380 ppm). CO₂-mediated rate increases were of similar relative magnitude in both phosphorus (P)-replete and P-limited cultures, suggesting that this effect may be independent of resource limitation. Neither isolate could grow at 15 Pa (150 ppm) CO₂, but N₂ and CO₂ fixation rates, growth rates, and nitrogen : phosophorus (N : P) ratios all increased significantly between 39 Pa and 152 Pa (1500 ppm). In contrast, these parameters were affected only minimally or not at all by a 4°C temperature change. Photosynthesis versus irradiance parameters, however, responded to both CO₂ and temperature but in different ways for each isolate. These results suggest that by the end of this century, elevated CO₂ could substantially increase global Trichodesmium N₂ and CO₂ fixation, fundamentally altering the current marine N and C cycles and potentially driving some oceanic regimes towards P limitation. CO₂ limitation of Trichodesmium diazotrophy during past glacial periods could also have contributed to setting minimum atmospheric CO₂ levels through downregulation of the biological pump. The relationship between marine N₂ fixation and atmospheric CO₂ concentration appears to be more complex than previously realized and needs to be considered in the context of the rapidly changing oligotrophic oceans.