[Objective] The most suitable granularity and scale for landscape analysis of the Yellow River Delta were determined, and spatiotemporal changes in landscape pattern vulnerability was analyzed in order to provide a theoretical basis for the sustainable use of land resources and environmental construction. [Methods] The landscape pattern index method and the coefficient of variation method were applied to Landsat remote sensing images from 2005, 2012, and 2018 to determine the most suitable spatial analysis granularity of the study area from the perspective of landscape level and type level. The grid method and geostatistical method were used to determine the most suitable spatial analysis scale. On this basis, the vulnerability indexes of the landscape pattern of the Yellow River Delta in the three study years were separately calculated, and the characteristics of their temporal and spatial evolution and spatial correlation characteristics were analyzed. [Results] ① During the two study periods (2005—2012, 2012—2018) construction land area in the Yellow River Delta increased by 10.1% and 10.0%, respectively, and unused land area changed by -7.7% and -9.4%; ② The most suitable granularity for the landscape analysis in the Yellow River Delta was 220 m, and the most suitable analysis scale was 3 km×3 km; ③ The vulnerability of landscape pattern gradually increased from the coastal area to the inland area. High-vulnerability areas were mainly located in the northern and eastern coastal areas, and the low-vulnerability areas were widely distributed across the central and southwestern regions; ④ Moran’s I coefficient increased over time, being 0.354, 0.365, and 0.399, in 2005, 2012, and 2018, respectively, indicating an increasingly obvious spatial aggregation of landscape pattern vulnerability. [Conclusion] During the study period, the vulnerability of the landscape pattern in the Yellow River Delta gradually deteriorated, and the spatial differences became more significant.