As a highly productive and biologically diverse ecosystem, wetlands provide unique habitat for a wide array of plant and animal species. Owing to the strong disturbance by human activities and climate change, wetland degradation and fragmentation have become a common phenomenon across the globe. The Guangdong–Hong Kong–Macao Greater Bay Area (GBA) is a typical case. The GBA has experienced explosive growth in the population and economy since the early 1980s, which has resulted in complicated transitions between wetlands and non-wetlands. However, our knowledge about the transformation paths, associated drivers, and ecological influence of the GBA’s wetlands is still very limited. Taking advantage of the land use maps generated from Landsat observations over the period of 1980–2020, here, we quantified the spatiotemporal transformation paths of the GBA’s wetlands and analyzed the associated drivers and ecological influence. We found that the dominant transformation path between wetland and non-wetland was from wetland to built-up land, which accounted for 98.4% of total wetland loss. The primary transformation path among different wetland types was from coastal shallow water and paddy land to reservoir/pond, with the strongest transformation intensity in the 1980s. The driving forces behind the wetland change were found to vary by region. Anthropogenic factors (i.e., population growth and urbanization) dominated in highly developed cities, while climate factors and aquaculture had a greater influence in underdeveloped cities. The findings presented in this study will provide a reference for wetland management and planning in the GBA.