Changes in the landscape structure of terminal lakes and wetlands along inland rivers in arid areas are determined by the water balance in the river basins under the impacts of climate change and human activities. Studying the evolution of these landscapes and the mechanisms driving these changes is critical to the sustainable development of river basins. The terminal lakes and wetlands along the lower reaches of the Heihe River, an inland river in arid northwestern China, can be grouped into three types: runoff-recharged, groundwater-recharged, and precipitation-recharged. These water-recharge characteristics determine the degree to which the landscape structure of a terminal lake or wetland is impacted by climate change and human activities. An analysis of seven remote-sensing and hydroclimatic data sets for the Heihe River basin during the last 50 years indicates that hydrological changes in the basin caused by regional human activities were the primary drivers of the observed changes in the spatial and temporal landscape-structure patterns of the terminal lakes and wetlands of the Heihe River. In this warm, dry climatic context, the lakes and wetlands gradually evolved toward and maintained a landscape dominated by saline-alkaline lands and grasslands.