Large carnivores can exert top–down effects in ecosystems, but the size of these effects are largely unknown. Empirical investigation on the importance of large carnivores for ecosystem structure and functioning presents a number of challenges due to the large spatio‐temporal scale and the complexity of such dynamics. Here, we applied a mechanistic global ecosystem model to investigate the influence of large‐carnivore removal from undisturbed ecosystems. First, we simulated large‐carnivore removal on the global scale to inspect the geographic pattern of top–down control and to disentangle the functional role of large carnivores in top–down control in different environmental contexts. Second, we conducted four small‐scale ecosystem simulation experiments to understand direct and indirect changes in food‐web structure under different environmental conditions. We found that the removal of top–down control exerted by large carnivores (> 21 kg) can trigger large trophic cascades, leading to an overall decrease in autotroph biomass globally. Furthermore, the loss of large carnivores resulted in an increase of mesopredators. The magnitude of these changes was positively related to primary productivity (NPP), in line with the ‘exploitation ecosystem hypothesis’. In addition, we found that seasonality in NPP dampened the magnitude of change following the removal of large carnivores. Our results reinforce the idea that large carnivores play a fundamental role in shaping ecosystems, and further declines and extinctions can trigger substantial ecosystem responses. Our findings also support previous studies suggesting that natural ecosystem dynamics have been severely modified and are still changing as a result of the widespread decline and extinction of large carnivores.