The ecological protection and high-quality development of the Yellow River Basin is a major strategic decision made by the Party Central Committee, and the scientific construction of a new pattern of land use and ecosystem in the Yellow River Basin is of great practical significance. This study starts from a relatively novel research perspective of landscape ecological vulnerability prediction in multiple scenarios, based on the analysis of land use type transfer in the Yellow River Basin from 1995 to 2020, for the four different development objectives of natural development, ecological protection, economic development, and coordinated development with ecological protection and economic development, the Genetic Algorithm (GA) optimization algorithm is coupled with the Patch-generating Land Use Simulation (PLUS) model to optimize the transfer probability of land use types, then simulate the spatial distribution of land use patterns, saline alkali land and wetlands in 2030, and calculated the landscape index and landscape ecological vulnerability on the basis of Land Use and Land Cover Change, and the evolution of ecological vulnerability characteristics of the Yellow River Basin were analyzed accordingly. The results showed that: (1) in the multi-scenario simulation of the LUCC in 2030, the forestland, grassland and water have increased to some extent in the four scenarios, and this demonstrates the effectiveness of ecosystem restoration; compared with other three scenarios, water expand the most in the coordinated development scenario, and the expansion rate of construction land is substantially lower than that of the natural development and economic development scenarios; (2) compared with 2020, salinization increases in 2030, with the most severe situation in the natural development scenario; the wetland ecosystem restoration effect is obvious, with the greatest degree of recovery in the coordinated development scenario; (3) the fragmentation of forestland, grassland, water and construction land in the Yellow River Basin in 2030 is weakened, while the opposite is true for cropland and unused land; compared to 2020, the overall landscape fragmentation of the basin has decreased, and the richness and diversity of land use has increased; (4) Compared with 2020, the landscape ecological vulnerability in the Yellow River Basin will continue to increase in 2030. The degree of deterioration is slower in the ecological protection scenario, and the coordinated development scenario is very effective for soil and water conservation in the wind-eroded areas of the upper watershed system and for ecological balance in the central plains. The results of this study provide a new theoretical foundation and practical evidence for land space planning and ecological protection in the Yellow River Basin.