Understanding the long-term (interannual-decadal) variability of water availability in river basins is paramount for water resources management. Here, the authors analyze time series of simulated terrestrial water storage components, observed precipitation, and discharge spanning 74 yr in the Colorado River basin and relate them to climate indices that describe variability of sea surface temperature and sea level pressure in the tropical and extratropical Pacific. El Niño-Southern Oscillation (ENSO) indices in winter [January-March (JFM)] are related to winter precipitation as well as to soil moisture and discharge in the lower Colorado River basin. The low-frequency mode of the Pacific decadal oscillation (PDO) appears to be strongly correlated with deep soil moisture. During the negative PDO phase, saturated storage anomalies tend to be negative and the "amplitudes" (mean absolute anomalies) of shallow soil moisture, snow, and discharge are slightly lower compared to periods of positive PDO phases. Predicting interannual variability, therefore, strongly depends on the capability of predicting PDO regime shifts. If indeed a shift to a cool PDO phase occurred in the mid-1990s, as data suggest, the current dry conditions in the Colorado River basin may persist.