Both global warming and human impacts are inimical to the maintenance of biodiversity across the planet. Although there is some consensus regarding the probable responses of biodiversity changes under different global change scenarios, the factors controlling biodiversity on regional scales are unclear. Using surveys of lake-bed surface sediments and an analysis of diatoms from six lake cores across 116 lakes in the southeastern Tibetan Plateau of China, we investigated (i) changes in diatom richness and (ii) β diversity and its components at various spatial and temporal scales. β diversity partitioning revealed that the most important factor affecting changes in diatom communities was species turnover across both spatial and temporal scales. This finding indicates that conservation planning requires a regional approach that focuses on multiple lake systems. Temporal changes in the trend of β diversity were shown to result from changes in nestedness components. The results showed that climate warming and indirect human impacts caused the decline of species nestedness, thereby increasing biodiversity, while the intensification of direct human activities caused species nestedness to rise, resulting in concomitant loss of biodiversity. Since nestedness is often related to ordered species gain/loss dynamics, the results suggest that species gain slows down in lakes affected indirectly by human activities, while species loss accelerates in lakes subjected to direct human impacts. Thus, we predict that species richness will continue to decline across this vast region in the future.