Jensen’s inequality predicts that the response of any given system to average constant conditions is different from its average response to varying ones. Environmental fluctuations in abiotic conditions are pervasive on Earth; yet until recently, most ecological research has addressed the effects of multiple environmental drivers by assuming constant conditions. One could thus expect to find significant deviations in the magnitude of their effects on ecosystems when environmental fluctuations are considered. Drawing on experimental studies published during the last 30 years reporting more than 950 response ratios (
n
= 5,700), we present a comprehensive analysis of the role that environmental fluctuations play across the tree of life. In contrast to the predominance of interactive effects of global-change drivers reported in the literature, our results show that their cumulative effects were additive (58%), synergistic (26%), and antagonistic (16%) when environmental fluctuations were present. However, the dominant type of interaction varied by trophic level (autotrophs: interactive; heterotrophs: additive) and phylogenetic group (additive in Animalia; additive and positive antagonism in Chromista; negative antagonism and synergism in Plantae). In addition, we identify the need to tackle how complex communities respond to fluctuating environments, widening the phylogenetic and biogeographic ranges considered, and to consider other drivers beyond warming and acidification as well as longer timescales. Environmental fluctuations must be taken into account in experimental and modeling studies as well as conservation plans to better predict the nature, magnitude, and direction of the impacts of global change on organisms and ecosystems.