With the 1999, 2004, 2011, and 2017 Landsat remote sensing images used as the main data sources, this study reveals the spatiotemporal evolution of wetland landscape characteristics of the Caizi Lake group from 1999 to 2017 and their relationships with human activities and socioeconomic factors by means of the grid analysis method, geodetector, and correlation analysis. Results are as follows: the artificial wetland area gradually increased while the natural wetland area gradually degraded; mudflats and herbaceous marshes showed a decreasing tendency, with proportions reducing by 12. 23% and 13. 84%, respectively, the areas of paddy fields and aquaculture ponds increased by 12. 12 km² and 20. 71 km², respectively, and the non-wetland area increased slightly; with the increase of the land use intensity, the landscape was more fragmented, the connectivity between patches became weak, the shape of wetland patches tended to be simplified, and the landscape heterogeneity increased. From 1999 to 2017, the wetland of the Caizi Lake group was significantly affected by human activities, and areas with high and relatively high intensities of human interferences dramatically expanded with time. Different human activities caused significant differences of impacts on the number of patches in time and space, and the interaction effect of human activities was even higher on the number of patches. The variation of wetland landscape indexes of the Caizi Lake group has close relationships with socioeconomic factors, including the output values of three industries, GDP, population, fishery production, and arable area.