Abstract: Investigating the influence of topography on regional land-use landscape patterns provides critical insights for understanding the dynamic patterns, processes, and effects of regional landscapes, thereby effectively guiding regional sustainable economic and social development and ecosystem conservation. This study investigated the Xiangtoushan area in Guangdong Province based on the interpretation results of five-period remote sensing images from 2000 to 2020. The dynamic changes in the land use of the Xiangtoushan area were explored from perspectives of topography and the distance from the nature reserve. The spatiotemporal variations of landscape indices were analyzed using the moving window method. The factors driving the landscape pattern changes in the Xiangtoushan area were examined using a geographic detector. The results show that over the 20 years, within the nature reserve, forest land maintained an absolute dominance and remained stable, with a variation amplitude of below 1.2%; water bodies remained stable overall except in 2005; and bare land exhibited an increase-to-decrease trend. Within the 10-km adjacent area from the natural reserve, the forest land area varied slightly, while the farmland area decreased by 14% and the construction land area increased by 67.2%. The landscape pattern within the natural reserve remained stable. In contrast, the 10-km adjacent area exhibited an overall landscape characterized by increasing fragmentation and complexity, with changes primarily occurring in the southern and northeastern parts. Elevation exerted the most significant influence on various landscape indices in the Xiangtoushan area, followed by slope gradient, whereas the distance from the nature reserve had the minimum influence. Notably, the restrictive effect of topography on the land-use landscape patterns in the Xiangtoushan area gradually weakened over time.