Anticipating ecosystem responses to global change requires identifying the isolated and combined effects of environmental disturbance across both space and time. Examining the coordinated responses of ecosystems has recently emerged as a powerful approach to advance this understanding. We conducted two complementary experiments to identify whether, and if so how, warming temperatures, nutrient enrichment, predator overexploitation (i.e., reduced apex predator abundance) and their combination drive coordinated responses of freshwater ecosystems by evaluating the dynamics of synchrony between control and disturbed mesocosms using high-frequency dissolved oxygen saturation measurements, an integrative parameter of the metabolic balance of ecosystems. Nutrient enrichment desynchronized the oxygen dynamics and their component cycles between treatments, likely arising from elevated primary production. Warming and overexploitation tended to desynchronize oxygen cycles from the control, particularly at short time scales. Nutrient enrichment combined with warming dampened desynchronization between control (ambient) and treatment mesocosms, whereas desynchronization was enhanced when simultaneously subject to predator overexploitation. As one of the first experimental demonstrations of global change impacts on ecosystem synchrony, this study highlights the need—and opens new avenues—to detect alterations in ecosystem functioning across previously unexplored spatial and temporal scales.