Fragmentation (establishment of barriers e.g., hydropower dams, reservoirs for irrigation) is considered one of the greatest threats to conservation of river systems worldwide. In this paper we determine the fragmentation status of central Chilean river networks using two indices, namely Fragmentation Index (FI) and Longest Fragment (LF). These are based on the number of barriers and their placement as well as river length available for fish movement. FI and LF were applied to eight Andean river basins of central Chile in order to assess their natural, current (2018) and future (2050) fragmentation at the doorstep of a hydropower boom. Subsequently, we exemplify the use of these indices to evaluate different placement scenarios of new hydropower dams in order to maximize hydropower use and at the same time minimize impact on fish communities. In the natural scenario 4 barriers (waterfalls) were present. To these 4 barriers, 80 new ones of anthropogenic origin were added in the current (2018) scenario, whereas 377 new barriers are expected in near future (2050). Therefore, compared to the ‘natural’ scenario, in 2050 we expect 115-fold increase in fragmentation in analysed river systems, which is clearly reflected by the increase of the FI values in time. At the same time, the LF diminished by 12% on average in the future scenario. The fastest increase of fragmentation will occur in small and medium rivers that correspond to 1st, 2nd and 3rd Strahler orders. Finally, case study on configuration of potential hydropower plants in the Biobío basin showed that hydropower output would be maximized and negative effects on fish communities minimised if new hydropower plants would be located in tributaries of the upper basin. Fragmentation of Chilean Andean river systems is expected to severely increase in near future, affecting their connectivity and ecological function as well as resilience to other anthropogenic stressors. Indices proposed here allowed quantification of this fragmentation and evaluation of different planning scenarios. Our results suggest that in order to minimise their environmental impact, new barriers should be placed in tributaries in the upper basin and river reaches above existing barriers.