This study analyses the changes in the runoff of forested experimental catchments in south-central Chile, to determine to what extent observed trends can be attributed to effects of intensive forestry and/or climate change. For this, we applied the distributed TETIS® model to eight catchments (7.1−413.6 ha) representative of the land uses and forestry activities in this geographical area. Rainfall and runoff data collected between 2008 and 2015 were used for modelling calibration and validation. Simulation of three land uses (current cover, partial harvest and native forest) and 25 combinations of climatic scenarios (percentage increases or decreases of up to 20% of rainfall and evapotranspiration relative to the no-change scenario applied to input series) were used in each calibration. We found that changes in land use and climate had contrasting effects on runoff. Smaller catchments affected by the driest climatic scenarios experienced higher runoff when the forest cover was lower than under full forest cover (plantations or native forests). In contrast, larger catchments under all climatic scenarios yielded higher runoff below the full forest cover than under partial harvest and native forest. This suggests that runoff can be influenced, to a great extent, by rainfall decrease and evapotranspiration increase, with the model predicting up to a 60% decrease in runoff yield for the dry’s climatic scenario. This study proves to be relevant to inform ongoing discussions related to forest management in Chile, and is intended to minimize the impact of forest cover on runoff yield under uncertain climatic scenarios.