Climate change has intensified the melting of glaciers and permafrost in high-altitude cold regions, leading to more frequent extreme hydrological events. This has caused significant variations in the spatiotemporal distribution of meltwater runoff from the headwater cryosphere, posing a major challenge to regional water security. In this study, the HBV hydrological model was set up and driven by CMIP6 global climate model outputs to investigate the multi-scale temporal variations of runoff under different climate change scenarios in the Tuotuo River Basin (TRB) within the source region of the Yangtze River (SRYR). The results suggest that the TRB will undergo significant warming and wetting in the future, with increasing precipitation primarily occurring from May to October and a notable rise in annual temperature. Both temperature and precipitation trends intensify under more extreme climate scenarios. Under all climate scenarios, annual runoff generally exhibits an upward trend, except under the SSP1-2.6 scenario, where a slight decline in total runoff is projected for the late 21st century (2061–2090). The increase in total runoff is primarily concentrated between May and October, driven by enhanced rainfall and meltwater contributions, while snowmelt runoff also shows an increase, but accounts for a smaller percentage of the total runoff and has a smaller impact on the total runoff. Precipitation is the primary driver of annual runoff depth changes, with temperature effects varying by scenario and period. Under high emissions, intensified warming and glacier melt amplify runoff, while low emissions show stable warming with precipitation dominating runoff changes.