The Ebinur Lake watershed is an important ecological barrier for environmental changes in the Junggar Basin in Xinjiang Uygur Autonomous Region (XUAR). Due to the tremendous changes in the underlying surface environment of the watershed in the past few decades, the watershed has become a typical region of ecological degradation. Drought affects the surface dynamics and characterizes the regional dry and wet environments, while the dynamic variation in lakes and vegetation are indicators of dynamic changes in land surfaces. Thus, a quantitative assessment of the response of lakes and vegetation to drought conditions at multiple temporal scales is critical for assessing the potential impacts of regional climate change on terrestrial ecosystems and ecological restoration. The standardized precipitation evapotranspiration index (SPEI), the spectral water index (NDWI) and the normalized difference vegetation index (NDVI) were used to analyse the evolution of drought, the variation in lake surface area and the sustainable variation in vegetation. Furthermore, we quantitatively evaluated the response patterns of vegetation to droughts of multiple temporal scales (1-, 3-, 6-, 12-, 24-month). The conclusions showed that (1) overall, the area of Ebinur Lake experienced drastic fluctuations, and the lake area has decreased significantly since 2003, with a dynamic area of 817.63 km2 in 2003 and 384.60 km2 in 2015, and the lake area had shrank severely. (2) The interannual variation of wet and dry changed alternately during the observation period, and persistent drought events occurred from 2006 to 2010 across the Ebinur Lake watershed. (3) The vegetation area of cultivated land expanded continuously across the watershed, and the grassland degraded severely. (4) The changes in lake surface area are significantly correlated with the inflow water volume (correlation coefficient = 0.64, P < 0.01). (5) The vegetation of different terrestrial ecosystems exhibited heterogeneous responses to multiple temporal scales of drought in different seasons. The percentage was 72.78% of the total area, which showed a correlation between vegetation and drought conditions during the growing season period, and there were more impacts of drought on vegetation, with values as high as 64.33% of the area in summer, than those in other seasons.