Vegetation phenology is widely used as an independent measure and powerful indicator of primary net productivity, crop yields, insect emergence, bird migration, climate change, carbon balance and cycle, and fundamental ecosystem function and is influenced at the local and global scales by climatic factors (including precipitation, temperature) and human activities. Studies of vegetation phenology are important, as solutions are needed to overcome issues such as environmental change, sustainable management, and biodiversity conservation. Hence, an in-depth understanding of the spatio-temporal variations and driving factors of vegetation phenology are important in the currently changing environment. The Bosten Lake Drainage Basin is located in northwest China and covers a vast area with a complicated terrain, including most of the middle Tianshan Mountains in the northwest, whole Yanqi basin, and northeast part of the Tarim basin in the south, which are characterized by distinctive distribution patterns of temperature, precipitation, and human activities. Here, based on the MCD12Q2, GHCN_CAMS air temperature, Digital Elevation Model(DEM), and metrological observed data, we established monthly geographical weighted regression (GWR) models and measured the near surface air temperature. Next, spatio-temporal evolution characteristics and driving factors of vegetation phenology in the Bosten Lake Drainage Basin were studied by determining slope, partial correlation, and multiple correlations. The results demonstrated that:(1) the start of growth season (SOG) was concentrated in 76-168 Julian days, whereas the end of growth season (EOS) was in 172-295 Julian days; the SOG was delayed and EOS was gradually advanced from north to south. Elevation played an important role in the regional differentiation of vegetation phenology; with increasing altitude, SOG was significantly delayed, EOG was advanced, and the length of the growth season (LOG) was significantly shortened. (2) SOG and EOG advanced synchronously in the plane oasis area during 2001 and 2014 because of the influence of human activities. (3) Climatic factors affected the area of SOG and BOG accounted for 57.10% and 51.30%, respectively, and was mainly located in the Huangshuigou river watershed, Qingshui river watershed, Konqi river watershed, Qongyultuz basin, and around the Kiqikyultuz basin. Non-climatic factors affected the area of SOG and BOG, accounting for 42.90% and 48.70%, and were located in low-altitude regions including the oasis around Bosten lake and the Korla oasis. (4) The correlation between vegetation phenology and climatic factors by partial correlation and multiple correlations demonstrated that variations in inter-annual SOG and BOG were mostly affected by air temperature. As altitude increased, vegetation showed obvious sensitivity of phenology to temperature. In summary, spatio-temporal variations in vegetation phenology in the Bosten Lake Drainage Basin are not only influenced by climate change, but are also influenced by the combined effects of human activities and altitude.