Globally, climate change has caused a significant reduction in snow cover in mountainous regions. To understand the impact of present and future snow changes on runoff in the semi-arid Andes, we applied the Hydro-BID hydrological model and associated datasets to the headwaters of the Elqui River basin (30°S) for current conditions and two Shared Socioeconomic Pathway (SSP) scenarios. Results show that model calibration at daily, monthly and annual time scales (R2 0.7, 0.7 and 0.8) and validation (R2 0.6, 0.7 and 0.7) were satisfactory. Future climate change scenario SSP2-4.5 indicates for 2040–2059, 2060–2079 and 2080–2099 temperature increases of 1.2, 1.6 and 1.9 °C and precipitation reductions of 26%, 29% and 36%. Discharge for SSP2-4.5 will reduce (the average annual flow decreases by 54%, 58% and 66%). For the same periods, SSP5-8.5 projects temperature increases of 1.5, 2.6 and 3.7 °C and precipitation reductions of 28%, 39% and 44%. Compared with SSP2-4.5, river discharge will experience a more acute reduction (projected annual decrease of 57%, 70% and 77%). Model results indicate that the maximum flow will be reached three months earlier than today. Results reinforce the importance of snow for runoff in the semi-arid Andes and the applicability of Hydro-BID in mountainous regions.