Under the influence of global climate change, the hydrological situation in the middle and upper reaches of the Jinsha River has changed greatly. It is of great significance to simulate the future runoff in these reaches for the better utilization of regional water resources. Based on the five global climate models (GCMs) of CMIP6, coupled with SWAT model and CA-Markov model, this study predicts the future runoff trends of the “carbon peak” period (2021-2040) and the “carbon neutrality” period (2041-2060), which can provide a theoretical support for the management and planning of water resources in the basin. The results show that the middle and upper reaches of the Jinsha River Basin present a warm and humid trend from 2021 to 2060, and the increase of temperature and rainfall is more significant under the “high carbon” pathway. In terms of land use change, except for the area of unused land which decreases in the future, the areas of other land use types all increase. Under the the scenario of “double carbon”, the annual runoff in the future shows an increasing trend, with the increasing rate of 155×106-201×106 m3/a for the “carbon peak” period, and 207×106-402× 106 m3/a for the “carbon neutrality” period; whereas under the “high carbon” scenario, the annual runoff shows a decreasing trend, with the decreasing rate of 99×106-107×106 m3/a for the “carbon peak” period and 85×106-106×106 m3/a for the “carbon neutrality” period. From the perspective of monthly average runoff, water resources are more abundant and more evenly distributed within the year under the “double carbon” scenario.