Global discharge regimes are strongly affected by multiple environmental drivers. It remains a challenge to relate their contributions and complex spatio-temporal cause-effect chains to a given time and location. To disentangle these relationships, we combined 12 environmental variables with changes in more than 25,000 discharge time series globally and identified the variable importance across climate zones using random forest analyses. The results show that (a) about two-thirds of the global catchments experienced significant changes in discharge between 1980s and 1990s and (b) more than 80% of the basins with new dams built during the study period have experienced changes, twice as many as basins without dams. Furthermore, (c) most environmental variables were subject to significant changes, especially precipitation, temperature and urban land cover; (d) strong changes in the discharge regime were mostly associated with precipitation, followed by land cover changes, and (e) impacts of water infrastructure are dominant in basins with weak evidence of change in discharge. Our findings highlight the contribution of each individual environmental factor on global discharge regimes and can be used to inform water-related studies and global modeling efforts in the future.