Based on Land Use and Cover Change (LUCC) and meteorological drought, comprehensively analysis of regional Groundwater Depth (GWD) change and its dynamic response, and clarifying the periodic leading factors of GWD change has practical significance for comprehensive management and effective control of groundwater resources in groundwater overexploitation area. Collecting the monthly-scale GWD data of 78 groundwater monitoring wells in the eastern plain area of Changji Prefecture from 2000 to 2020 and five phases of remote sensing image data, and combing with the multi-scale Standardized Precipitation Evapotranspiration Index (SPEI) during the contract period, the dynamic response of GWD at different spatial and temporal scales to LUCC and SPEI were analyzed, and the comprehensive influence of land use change and drought change trend on the change of GWD in the study area was discussed. The results showed that during the 21 years from 2000 to 2020, the GWD in the study area showed the change characteristics of no significant indigenous change (2000-2005)-significant indigenous increasing (2005-2014)-slowing down (2014-2017)-continuous increasing (2017-2020). The overall trend was increasing continuously, the spatial distribution gradually increased from north to south. During the same period, the area of land use types changed significantly. Cropland was the main land use type, and its area increased continuously. The fractal dimension showed the change characteristics of first decreasing (2000-2005) then increasing (2005-2010), and then decreasing (2010-2020). The interannual dynamic change of SPEI showed a significant trend of indigenous drought. The annual-scale sequence mutated in 2012 and 2017, and the frequency of meteorological drought increased since 2016. From 2000 to 2015, the dynamic change of GWD in the study area responded significantly to land use change, especially cultivated land change. From 2016 to 2020, the dynamic change of GWD was a joint response to land use change and meteorological drought factors.