[Objective] The spatial and temporal evolution characteristics of habitat quality and the spatial mechanism of influencing factors in Anhui Province were analyzed in order to provide a basis for improving the ecological management ability and sustainable development ability of the study area. [Methods] The InVEST model was used to analyze the spatial and temporal pattern evolution of habitat quality in Anhui Province from 2000 to 2020. A multi-scale geographical weighted regression (MGWR) model was used to analyze the spatial mechanisms of natural, socio-economic, landscape, and other factors on habitat quality. [Results] ① Cultivated land was always the dominant landscape in Anhui Province from 2000 to 2020, and landscape transformation in the region mainly occurred between cultivated land, forest land, and construction land. The expansion of the landscape elements of construction land was the most obvious. With the increase of disturbance degree of human activities, the landscape pattern of Anhui Province was evolving towards fragmentation and complexity. ② From 2000 to 2020, the average value of habitat quality in Anhui Province decreased by 0.016, showing a slight degradation trend on the whole. The habitat quality in the region was mainly poor (0.2~0.4), and the two periods accounted for more than 40% of the data. There were obvious spatial differences in the habitat quality of Anhui Province, showing a spatial pattern of “higher in the south and lower in the north”. ③ According to the regression results of the MGWR model, rainfall and normalized vegetation index had significant positive effects on the habitat quality of Anhui Province, and the positive proportion of the regression coefficients in the two periods was greater than 80%, and further expanded with time. In terms of the spatial pattern, the regression coefficient of Southern Anhui Province was larger than that of Northern Anhui Province. Population density and GDP per unit area had significant negative effects on habitat quality in Anhui Province. The negative ratio of regression coefficients in both periods was greater than 90%, and the regression coefficient in Northern Anhui Province was larger than in Southern Anhui Province. The maximum patch index and the evenness index had positive and negative bidirectional effects on the habitat quality in Anhui Province. With the development of fragmentation and complexity of the landscape pattern in Anhui Province, the negative proportion of the regression coefficient further expanded. [Conclusion] The spatial pattern of habitat quality in Anhui Province presented a certain pattern. On this basis, combined with the analysis results of influencing factors, differentiated protection policies should be formulated to manage the ecological environment according to local conditions in order to improve the sustainable development ability of Anhui Province and to achieve the goal of harmonious coexistence between man and nature.