With increasing human activity and climate change, the arid lakes of northwest China have exhibited increased eutrophication and salination trends in recent years. As important indicator species, diatoms are widely used to explain past environment changes. The aims of this study were to describe the succession of the sediment diatom community in the large arid Bosten Lake and to discuss the responses of the diatoms to human activities and climate change over recent history. Sediment diatom analysis was applied to short core sediment samples extracted from the river mouth and the deep centre of Bosten Lake. The diatom assemblages were dominated by Cyclotella praetermissa, Fragilaria crotonensis and small fragilarioid and periphytic taxa. These diatom taxa are interpreted as being sensitive to changes in the water level and trophic status in the water column, which are probably related to the climate and human activities. The high percentage of Cyclotella praetermissa suggests that the water level was higher prior to the 1860s. From the 1860s to the 1950s, Aulacoseira alpigena appeared in the profundal zone, which indicates that spring winds may have been stronger. The high percentage of Navicula oblonga in the river mouth zone revealed that the lake might have been slightly brackish. From the 1950s to the early 1980s, the percentage of planktonic diatoms decreased, and F. crotonensis appeared, which indicates that the water level was lower and that human activity had increased. From the 1980s to the end of the 20th century, the population, land cultivation, and fish production all increased, resulting in changes in salinity and a rapid decline in water levels. During this period, the diatoms at the river mouth of the Kaidu River were dominated by benthic species, and the deepest site of the lake was dominated by F. crotonensis. Since the 20th century, F. crotonensis has been dominant as the water level has increased and the trophic status has changed in the lake. Environmental changes in the Bosten Lake catchment affected the diatom assemblage in the profundal zone much earlier than in the river mouth zone. The patchiness of the diatom distribution within the lake macroenvironment indicates the influence of microenvironments on diatom community structure. Over the last several decades, human activities may have caused the ecosystem of Bosten Lake to exceed a threshold and collapse into a new state.