A high-quality daily runoff time series of the Lake Como inflow and outflow, the longest for Italian Alps, was reconstructed for the 1845-2016 period in the Adda river basin. It was compared with contemporary monthly precipitation and temperature observations and estimated potential evapotranspiration losses. Trend analyses were conducted for daily flow maxima and 7-day duration minima of inflows into the lake showing a non-significant decrease and a significant increase, respectively. Although the annual precipitation time series exhibits a non-significant decrease, annual runoff volumes decrease with a rate of −136 mmÁcentury −1 , with a significance level of 5%. Possible causes of variability of rainfall and runoff as North Atlantic Oscillation (NAO), Atlantic Multidecadal Oscillation and Western Mediterranean Oscillation indexes and sunspot activity were also explored. Wavelet spectra analyses of monthly precipitation and runoff show some changes in the energy both at small and large scales and are effective in pointing out phenomena as droughts and the effects of dams' regulation. Conversely, wavelet coherence spectra indicate a weak correlation of NAO and sunspots with precipitation. In addition, the analysis of temperature and potential evapotranspiration tendencies suggests that the decrease of runoff has to be ascribed mostly to anthropogenic factors, including water abstraction for irrigation and increased evapotranspiration losses due to natural afforestation and, only in part, to climatic variability.