This research focuses on the statistical analyses of hydrometeorological time series in the basin of Lake Tana, the largest freshwater lake in Ethiopia. We used autocorrelation, cross-correlation, Mann–Kendall, and Tukey multiple mean comparison tests to understand the spatiotemporal variation of the hydrometeorological data in the period from 1960 to 2015. Our results show that mean annual streamflow and the lake water level are varying significantly from decade to decade, whereas the mean annual rainfall variation is not significant. The decadal mean of the lake outflow and the lake water level decreased between the 1990s and 2000s by 11.34 m3/s and 0.35 m, respectively. The autocorrelation for both rainfall and streamflow were significantly different from zero, indicating that the sample data are non-random. Changes in streamflow and lake water level are linked to land use changes. Improvements in agricultural water management could contribute to mitigate the decreasing trends.