The ecosystems on the northern slope of the Tianshan Mountains is fragile and vulnerable to drought. Global warming and damaging human activities exacerbate the effects of drought. Here, we assess the response of the vegetation cover to drought, and provide a scientific basis for improving the ecological environment and mitigating the effects of drought. Based on the normalized difference vegetation index of the moderate resolution imaging spectroradiometer (MODIS-NDVI) and meteorological observation data, standardised precipitation-evapotranspiration index (SPEI) and vegetation coverage on the northern slope of the Tianshan Mountains were calculated. Then, the temporal and spatial dynamics of vegetation coverage and multi-scale SPEI over the period from 2001 to 2015 were analyzed. Finally, in the perspective of land-use and land-cover change (LUCC), the correlation between them is discussed. The experimental results demonstrated that most of the northern slope of the Tianshan Mountains is in a humid state, with mild drought in the central (Shihezi, Hutubi) and northwest (Kenamayi) regions. The SPEI of three, six, and twelve months showed an inter-annual variation trend of enhanced aridificationt. The vegetation coverage of the northern slope in Tianshan Mountains was generally low to medium, of which with higher coverage level in the mountains and urban oases, with the overall height trend being high in the south and low in the north. From 2001 to 2015, the vegetation coverage of the northern slope of the Tianshan Mountains showed a downward trend, and this was positively correlated with drought. The vegetation coverage of different land-use and land-cover types was different from SPEI 12, and the order was:grassland > unutilized land > urban and rural land > forest land > water area > cultivated land. The influence of drought on vegetation coverage in summer and spring is the most obvious seasonal effect. The drought in different seasons had different degrees of influence on vegetation coverage of different land-use and land-cover types.