The management of regional eco-environmental risks is the key to promoting regional economic sustainability from the macro level, and accurate evaluation of the evolutionary trends of regional ecological risk in the future is of high importance. In order to clearly identify the possible impact of future development scenario selection for the Chengdu-Chongqing Economic Zone (C-C E Zone) on the evolution of landscape ecological risk (LER), we introduced the Patch-generating Land Use Simulation (PLUS) model to simulate land use data for the C-C E Zone from 2030 to 2050 for two scenarios: natural development (ND) and ecological protection (EP). Based on the ecological grid and landscape ecological risk index (LERI) model, the landscape ecological risk (LER) evolutionary trends seen in the C-C E Zone from 2000 to 2050 were analyzed and identified. The results showed that: (1) The PLUS model can obtain high-precision simulation results in the C-C E Zone. In the future, the currently increasing rate of land being used for construction will be reduced, the declining rates of forest and cultivated land area will also be reduced, and the amount of land being used for various purposes will remain stable going into the future. (2) This study found that the optimal size of the ecological grid in the LERI calculation of the mountainous area was 4 × 4 km. Additionally, the mean values of the LERI in 2030, 2040, and 2050 were 0.1612, 0.1628, and 0.1636 for ND and 0.1612, 0.1618, and 0.1620 for EP. (3) The hot spot analysis results showed that an area of about 49,700 km2 in the C-C E Zone from 2000 to 2050 belongs to high agglomeration of LER. (4) Since 2010, the proportions of high and extremely high risk levels have continued to increase, but under the EP scenario, the high and extremely high risk levels in 2040 and 2050 decreased from 14.36% and 6.66% to 14.33% and 6.43%. Regional analysis showed that the high and extremely high risk levels in most regions increased over 2010–2050. (5) Under the ND scenario, the proportions of grids with decreased, unchanged, and increased risk levels were 15.13%, 81.48%, and 3.39% for 2000–2010 and 0.54%, 94.75%, and 4.71% for 2040–2050. These trends indicated that the proportion of grids with changed risk levels gradually decreased going into the future. This study analyzed the evolutionary trends of LER at the C-C E Zone for the ND and EP scenario. On the whole, the LER for the C-C E Zone showed an upward trend, and the EP scenario was conducive to reducing the risk. These research results can serve as a valuable data reference set for regional landscape optimization and risk prevention and control.