Due to intense human activity and landscape configuration changes, evaluating habitat quality is critical for ecosystem service capacity maintenance while promoting human well-being. This study aimed to evaluate and analyze the temporal and spatial responses of landscape patterns to habitat quality changes in the Poyang Lake region. During 2000–2020, the landscape pattern in the Poyang Lake region shifted from agglomeration to fragmentation. Within this period, the area with the highest proportion of habitat quality reached a poor level within the region, and the area with the worst level experienced notable improvement. The concentration of excellent habitat quality areas was evident within the central region of Poyang Lake, as well as in the northeastern and northwestern of the entire region. The proportion of habitat quality improvement surpassed that of habitat degradation, accounting for 32.62% and 17.94%, respectively. Notably, areas characterized by moderate and good habitat quality experienced a significant upgrade to an excellent level by 2020. The results of spatial autocorrelation, as measured by Moran's I index, indicated a consistent positive trend. This value gradually increased over time, suggesting a progressive intensification in the spatial clustering of habitat quality. Furthermore, the spatial heterogeneity in habitat quality was primarily driven by CONTAG, which was the primary influential factor. An enhanced two-factor interaction, surpassing the explanatory force of the factors on their own, was observed through an analysis of the interactions between different combinations of influencing factors. The explanatory force of the CONTAG index indicated a decline in habitat quality in certain local regions. For these areas, we suggest controlling the disorderly development of construction land and transportation systems, strictly prohibiting the illegal occupation of arable land, promoting vegetation restoration, and maintaining landscape patch connectivity.