Vegetation phenology is considered a sensitive indicator of terrestrial ecosystem response to global climate change. We used a satellite-derived normalized difference vegetation index to investigate the spatiotemporal changes in the green-up date over the Three-Rivers Headwater Region (TRHR) from 1999 to 2013 and characterized their driving forces using climatic data sets. A significant advancement trend was observed throughout the entire study area from 1999 to 2013 with a linear tendency of 6.3 days/decade (p < 0.01); the largest advancement trend was over the Yellow River source region (8.6 days/decade, p < 0.01). Spatially, the green-up date increased from the southeast to the northwest, and the green-up date of 87.4% of pixels fell between the 130th and 150th Julian day. Additionally, about 91.5% of the study area experienced advancement in the green-up date, of which 80.2%, mainly distributed in areas of vegetation coverage increase, experienced a significant advance. Moreover, it was found that the green-up date and its trend were significantly correlated with altitude. Statistical analyses showed that a 1-°C increase in spring temperature would induce an advancement in the green-up date of 4.2 days. We suggest that the advancement of the green-up date in the TRHR might be attributable principally to warmer and wetter springs.