The quantitative attribution of changes in streamflow to climate change (CC) and land cover change (LCC) for the Yangtze River Source Region (YRSR), China, was assessed. We used a combination of the SWAT model along with the statistical technique one factor at a time (OFAT) and innovative trend analysis (ITA) to achieve the study objectives. The climate and hydrology data from 1961 to 2016 and land-cover maps of 5 years’ difference from 1985 to 2015 were used. The model was calibrated (1964–1989) using a land-cover map of 1985 and validated for 1990–2016. This validated model was further validated for all other land-cover maps used in this study. The SWAT model simulation showed that streamflow had been significantly influenced by CC compared to LCC using land-cover maps of 1985–1990, 1990–1995. However, the SWAT model simulations did not result in further changes in streamflow for land cover maps of 2000–2005, 2005–2010, and 2010–2015 because there have not been any significant changes in land cover after 2000 while the main contributing factor was climate change. The SWAT model simulations showed that the main driver of changes in streamflow in the Yangtze River Source Region is climate change. This study shows that the individual impacts are more critical than combined impacts for designing hydraulic structures, water resources planning and management, and decision-making policies at the regional/basin scale.