The water-town settlements in the East River Delta of China engage with the aquatic environment, establishing a comprehensive cultural–ecological system. However, rapid urbanization challenges the structural integrity of water-town settlements. Focusing on the East River Delta as the study area, we utilized the Normalized Difference Water Index (NDWI), settlement morphology indicators, systematic clustering, and graph classification methods. We conducted a quantitative analysis of the spatial characteristics of water-town settlements at various scales, followed by formulating a sequence encoding based on landscape factors and constructing a settlement landscape spatial map. We characterized the landscape spatial structure of water-town settlements formed through the gradual evolution of morphological water network structures, retracing a prototype of water-town settlement landscape spatial structures. Results: ① Water-town settlements exhibit distinct uniformity in the landscape spatial features. The settlement landscapes conform to water network patterns, with streets and alleys aligning with water bodies. Crucial elements, including docks, bridges, and waterside farmland, are integral to this landscape. ② Water-town settlements undergo three progressive differentiation phases based on their location. The spatial distribution of settlements reveals three distinct landscape features influenced by the delta’s dynamic interplay between water and land. ③ Various regions exhibit three typical settlement layouts: upstream settlements are mainly clustered and linear, while midstream and downstream settlements, characterized by linear and strip-like features, align with the river’s course. These research findings offer preliminary insights into landscape spatial prototypes, contributing valuable perspectives to the conservation and design of water-town settlements.