As an important ecological resource in coastal zones, tidal flats are of great significance for environmental protection and regional sustainable development. Additionally, tidal flats are sentinels of regional and global changes and thus have recently become a focus of academic research. However, the accessibility of tidal flats is poor because tidal waters periodically inundate them. This makes it difficult to employ traditional measurements to monitor such highly dynamic environments. Accordingly, remote sensing observation has become a potential choice. Yet, remote sensing observations also face great challenges because of influences from imaging modes, atmospheric conditions, and tide conditions. For this research, we selected the Yangtze River Delta, which is covered by a single full scene of Landsat image, as the study region, specifically including parts of the Jiangsu coast and the Yangtze River estuary zone. A collection of the Landsat images with the lowest tidal level in each year from 1975 to 2017 was selected as the main data sources. Meanwhile, to extract tidal flat data, we choose the waterline as the outer boundary and the vegetation line or reclamation dyke as the inner boundary. Then, ArcGIS software was used to acquire and analyze the temporal and spatial variability of the tidal flat data. The results show the following: (1) The tidal flat area in the study region has generally decreased since 1975. The area remained generally stable before 1990s, but after 1990s, the decline was evident. The tidal flat areas along the north of the Yuantuojiao Point and the Yangtze River estuary zone reached their maximums around 1995, at 1101.2 km~2 and 1495.5 km~2, respectively, but were 649.5 km~2 and 1043.4 km~2 by 2017. This indicates an overall decreasing rate of 21.7 km~2/a. (2) Reduced riverine sediment, reclamation, and estuarine engineering projects, such as the Deep-water Navigation Channel project, are the main controlling factors in tidal flat shrinkage in the study region. The results provide a holistic perspective on the evolution of the tidal flats in the Yangtze River Delta, which may be helpful for coastal zone management and planning.