The Ordovician-Silurian transition was a critical interval in Earth's history marked by dramatic climatic, oceanic, and biological turnovers. Here we present the chemical index of alteration (CIA) as a proxy of changes in intensity of chemical weathering, and its variations across the Ordovician-Silurian boundaries (Wufeng through Guanyinqiao, to Longmaxi Formations) from Wangjiawan and Nanbazi on the Yangtze block, south China, in order to explore the climatic changes. Our data show that the CIA values of sediments commonly range from 75 to 90 in the Wufeng and Longmaxi Formations, indicating a high degree of chemical weathering and thus a hot and humid climate during deposition. In contrast, a sharp drop in CIA values (most 60–70) in the Guanyinqiao Formation (or Hirnantian) suggests an overall cold and arid climate, interrupted by several intervals of warm climate when deposited. The temporal coincidence of two phases of massive biotic extinctions with the beginning and end of the cold climate epoch, respectively, suggests that the large climatic changes could be one of the main controls on the mass extinctions, although other factors may also have played a role.