Amazonian deforestation has accelerated during the last decade, threatening an ecosystem where almost one third of the regional rainfall is transpired by the local rainforest. Due to precipitation recycling, the southwestern Amazon, including the Amazon-Andes transition region, is particularly sensitive to forest loss. This study evaluates the impacts of Amazonian deforestation on the hydro-climatic connectivity between the Amazon and the eastern tropical Andes during the austral summer (December–January–February) in terms of hydrological and energetic balances. Using 10-years high-resolution simulations (2001–2011) with the Weather Research and Forecasting Model, we analyze control and deforestation scenario simulations. Regionally, deforestation leads to a reduction in the surface net radiation, evaporation, moisture convergence and precipitation (~ 20%) over the entire Amazon basin. In addition, during this season, deforestation increases the atmospheric subsidence over the southern Amazon and weakens the regional Hadley cell. Atmospheric stability increases over the western Amazon and the tropical Andes inhibiting convection in these areas. Consequently, major deforestation impacts are observed over the hydro-climate of the Amazon-Andes transition region. At local scale, nighttime precipitation decreases in Bolivian valleys (~ 20–30%) due to a strong reduction in the humidity transport from the Amazon plains towards the Andes linked to the South American low-level jet. Over these valleys, a weakening of the daytime upslope winds is caused by local deforestation, which reduces the turbulent fluxes at lowlands. These alterations in rainfall and atmospheric circulation could impact the rich Andean ecosystems and its tropical glaciers.