Built-up land changes along slope gradients (BCSG) are widespread globally, driven by natural environmental and socio-economic variations. This process has profound effects on vegetation cover and is closely related to the United Nations Sustainable Development Goals. However, the mechanisms involved in the BCSG remain to be elucidated, and the impacts of BCSG on vegetation cover need to be quantified. The BCSG from 1990 to 2020 was described through slope spectrum analysis by taking the Three Gorges Reservoir Area (TGRA) as an example. Then, the Normalized Difference Vegetation Index (NDVI) was used as an indicator of vegetation cover, and its influence by BCSG was explored through a multiple linear regression model. The built-up land in the TGRA from 1990 to 2020 was first dominated by slope climbing (SC) and then by horizontal expansion, and the intensity of built-up land SC showed a general trend of weakening over time. During the 30 years, the intensity of built-up land SC weakened and then strengthened in townships with mainly intermountain plains, while gradually decreasing in townships with mainly hills and townships with mainly mountains. Socio-economic factors, natural factors, and regional special events drive the BCSG in TGRA. Built-up land SC in the TGRA will have a negative impact on NDVI but to a progressively lesser degree from 1990 through 2020. The built-up land SC in townships with mainly hills and mountains has a negative effect on NDVI. The built-up land SC in townships with mainly intermountain plains has a positive impact on NDVI. These results can provide a scientific basis for formulating reasonable vertical management policies for built-up land and help reduce the ecological risks caused by land development.