As patterns of precipitation and evapotranspiration change, human water security and aquatic ecosystem health depend on understanding how catchment characteristics interact with climate to control river flow and water budget imbalances. We compiled estimates of precipitation, actual and potential evapotranspiration, temperature, and river discharge for over 1,148 catchments during the 2001-2020 period and used these estimates to calculate water budget imbalances as well as changes in runoff ratio and numerous river flow properties including timing, magnitude, and variability of flow. We found that that the parameter from Fuh’s equation (m) was a powerful predictor of hydrologic sensitivity to climate fluctuations, but not necessarily the magnitude of these changes. Specifically, water budget imbalances were almost entirely explained by two catchment properties: m and aridity. Runoff ratio sensitivity to temporal fluctuations in wetness index were also best explained by m, compared to a host of other catchment characteristics tested. In contrast to its predictive power for sensitivity, m was a poor predictor of total changes in runoff ratio. A subsequent correlational analysis between changes in runoff ratio and 66 geographic, climatic, land use, and human impact metrics, found that fluctuations in climate were a far more powerful predictor of changes in runoff ratio (and a suite of other flow properties) than m, indicating that at the global scale, the magnitude of changes in climate dominate the idiosyncratic catchment-level responsiveness to changes in climate, emphasizing the paramount importance of addressing climate change in protecting freshwater resources.