Global warming has generally led to changes in river runoffs fed by snow and glacier meltwater in mountain ranges. The runoff of the Aksu River, which originates in the Southern Tienshan Mountains, exhibited a positive trend during 1979–2002, but this trend reversed during 2002–2015. Through a comprehensive analysis, this study aims to estimate potential reasons for changes in the runoff of its two contrasting headwaters: the Toxkan and Kumalak Rivers, based on climatic data, the altitude of the 0 °C isotherm, glacier mass balance (GMB), snow cover area (SCA), snow depth (SD) and the sensitivity model. For the Toxkan River, the decrease in spring runoff mainly resulted from reductions in precipitation, whereas the decrease in summer runoff was mainly caused by early snowmelt in spring and a much-reduced snow meltwater supply in summer. In addition, the obvious glacier area reduction in the catchment (decreased to less than 4%) also contributed to the reduced summer runoff. For the Kumalak River, a sharp decrease rate of 10.21 × 108 m3/decade in runoff was detected due to summertime cooling of both surface and upper air temperatures. Reduced summer temperatures with a positive trend in precipitation not only inhibited glacier melting but also dropped the 0 °C layer altitude, resulting in a significant increase in summertime SCA and SD, a slowing of the glacier negative mass balance, and a lowering of the snow-line altitude.