The effects of climate change projected for 2050 to 2079 relative to the 1968–2014 reference period were evaluated using 39 CMIP5 models under the RCP8.5 emissions scenario in the Guayas River basin. The monthly normalized precipitation index (SPI) was used in this study to assess the impact of climate change for wet events and droughts from a meteorological perspective. The GR2M model was used to project changes in the streamflow of the Daule River. The climate projection was based on the four rigorously selected models to represent the climate of the study area. On average, an increase in temperature (~2◦C) and precipitation (~6%) is expected. A 7% increase in precipitation would result in a 10% increase in streamflow for flood periods, while an 8% decrease in precipitation could result in approximately a 60% reduction in flow for dry periods. The analysis of droughts shows that they will be more frequent and prolonged in the highlands (Andes) and the middle part of the basin. In the future, wet periods will be less frequent but of greater duration and intensity on the Ecuadorian coast. These results point to future problems such as water deficit in the dry season but also increased streamflow for floods during the wet season. This information should be taken into account in designing strategies for adaptation to climate change.