The Oriental migratory locust is a destructive agricultural pest in China. Large-scale locust area (the area possessing suitable breeding habitat for locusts and has locust infestation) extraction and its evolution analysis are essential for locust ecological control. Existing methods seldom consider the spatial differences in the locust development and habitat landscape structures in large areas. To analyze these effects, our study proposed a landscape-based habitat suitability model (LHS model) for large-scale locust area extraction based on remote sensing data, taking the middle and lower reaches of the Yellow River (MLYR) as an example. Firstly, the DD model was used to simulate locust development and obtain habitat factors of the corresponding dates; secondly, the patch distribution of different land cover classes and their adjacent landscape characteristics were analyzed to determine the landscape-based factors memberships; finally, the habitat suitability index was calculated by combining the factors memberships and weights to extract the locust area. Compared with the patch-based model using moving windows (patch based-analytic hierarchy process model, R2 = 0.77), the LHS model accuracy improved significantly (R2 = 0.83). Our results showed that the LHS model has a better application prospect in large-scale locust area extraction. By analyzing the locust areas evolution along the MLYR extracted using the LHS model, we found human activities were the main factors affecting the locust areas evolution from 2016 to 2020, including: (1) planting the plants that locusts do not like and urbanization caused the decrease of the locust area; (2) the wetland protection policies may cause the increase of the locust area. The model and research results help locust control and prevention to realize the sustainable development of agriculture.