Most of the previous studies exploring the changing patterns of wetland in the Yellow River Delta (YRD) were conducted based on sparse time-series images, which ignored its severe environmental gradient and rapid evolution process of the wetland. The changes in the dominant factors in the evolution of the wetland in the YRD are not clear. This study used the dense time-series Sentinel-2 images to establish a wetland database of the YRD, and then analyzed the spatial distribution characteristics of, and temporal changes in, the wetland during 2015–2022. Finally, the dominant factors of the spatio-temporal evolutions of the wetland were explored and revealed. The results showed the following. (1) During 2015–2022, the wetland in the YRD was dominated by artificial wetland, accounting for 54.02% of the total wetland area in the study area. In 2015–2022, the total wetland area increased by 309.90 km2, including an increase of 222.63 km2 in natural wetlands and 87.27 km2 in artificial wetlands. In the conversion between wetland types, 218.73 km2 of artificial wetlands were converted into natural wetlands, and 75.18 km2 of natural wetlands were converted into artificial wetlands. The patch density of rivers, swamps, and salt pans increased, showing a trend of fragmentation. However, the overall degree of landscape fragmentation in wetlands weakened. The trend of changes in the number of patches and landscape shape index was the same, while the trend of changes in Shannon’s diversity index and Contagion index was completely opposite. (2) Natural factors, such as precipitation (0.51, 2015; 0.65, 2016), DEM (0.57, 2017; 0.47, 2018; 0.49, 2020; 0.46, 2021), vegetation coverage (0.59, 2019), and temperature (0.48, 2022), were the dominant influencing factors of wetland changes in the YRD. The dominant single factor causing the changes in artificial wetlands was vegetation coverage, while socio-economic factors had lower explanatory power, with the average q value of 0.18. (3) During 2015–2022, the interactions between the natural and artificial factors of the wetland changes were mostly nonlinear and showed double-factor enhancement. The interactions between temperature and sunshine hours had the largest explanatory power for natural wetland change, while interactions between precipitation and vegetation coverage, and between temperature and vegetation coverage, had large contribution rates for artificial wetland change. The interactions among natural factors had the greatest impacts on wetland change, followed by interactions between natural factors and socio-economic factors, while interactions among socio-economic factors had more slight impacts on wetland change. The results can provide a scientific basis for regional wetland protection and management.