Abstract: Land-use change is an important manifestation of interactions between humans and nature and is jointly influenced by multiple factors. Existing research has paid little attention to spatial scales and lacks in-depth analysis of the driving mechanisms and future changes. Therefore, based on land-use data from 2000 to 2020, this study systematically analyzed the spatiotemporal evolution characteristics and driving factors of land use in the Chengdu-Chongqing urban agglomeration by comprehensively applying land use dynamics, transfer matrices, optimal parameter geographic detectors, and PLUS models. Furthermore, it simulates future land use under multiple scenarios. The results showed that: (1) From 2000 to 2020, cultivated land in the Chengdu-Chongqing urban agglomeration decreased by 382 619.79 hm², while construction land expanded rapidly by 436 111.92 hm². revealing a pronounced pattern of “sharp decline in arable land coupled with rapid growth in construction land”. Spatially, this expansion exhibited a “dual-core driven” pattern centered on the main urban areas of Chengdu and Chongqing. (2) Among natural factors, slope and precipitation exerted sustained significant influences on land-use changes. Among accessibility factors, distance from water systems was a consistently significant driver. For socio-economic factors, the explanatory power of GDP and population density increases over time. Importantly, the interactive effects among factors are significantly stronger than the independent effects of any single factor. (3) Under the natural development scenario, construction land expands in an unregulated manner. The cultivated land protection scenario ensures food security by curbing the loss of farmland, while the ecological protection scenario balances ecological security with urban development. The findings suggest that strengthening farmland protection policies, optimizing urban spatial layouts, advancing ecological restoration projects, and promoting regional coordinated development are essential pathways for the Chengdu-Chongqing urban agglomeration to achieve sustainable land-use and high-quality regional development.