In this study, wetlands in the Ili River Delta (IRD) from 1975 to 2020 were extracted based on Landsat images using the object-oriented method; changes in the wetland area, wetland landscape pattern, NDVI and NPP were analyzed; and the contributions of natural and human factors to wetland evolution were quantified. The results indicated that (1) From 1975 to 2020, the wetland area of the IRD showed an increasing trend, and changes in the wetland area were mainly found in the middle part of the delta near the Saryesik Peninsula. (2) The wetland landscape pattern in the IRD changed markedly from 1975 to 2020. The dominant patches of the wetland in the middle of the delta continued to expand; the patch aggregation index (AI) increased, and the patch fragmentation index (LFI) decreased. (3) From 2000 to 2020, the average annual normalized difference vegetation index (NDVI) and net primary productivity (NPP) in the IRD increased, which is consistent with the change in wetland expansion. (4) Inflow to the delta from the Ili River and the water level of Balkhash Lake are significantly correlated with the wetland area, which are the dominant factors driving wetland evolution; and water evaporation from the Kapchagay Reservoir and irrigation water diversion on the left bank of the reservoir obviously intensified the process of lake water level decline and wetland degradation during 1970 to 1985. These results can provide scientific background for making informed ecological protection decisions in the Ili River Delta under the impacts of climate change and human activities.