Chemical weathering in the Himalayan river basins is among the highest in the world and has received vast research attention related to past climate change. Many early estimates of chemical weathering are based on a small number of water property data that ignore those spatial and seasonal variations. Therefore, this study analyzed spatial and seasonal variations in chemical weathering in the Mekong Basin, where the geology, climate, and hydrologic cycle of the basin vary significantly from the lower to upper reaches and from dry to rainy seasons. We separately estimated the origins of dissolved elements and potential CO2 consumption rates using the numerous chemical compositions of river water throughout the entire basin and in both seasons. The CO2 consumption rate in the rainy season is three to five times that in the dry season that may be due to the high temperature and precipitation. Despite the low temperatures and dryness of the upper and middle basins, the CO2 consumption rate is approximately twice that in the lower reaches; this can be attributed to active physical denudation in steep mountainous areas which increases the surface area for water-rock interactions. The total CO2 consumption obtained by combining each season and basin was 48-70 x 10(9) mol/a and 148-159 x 10(9) mol/a for silicate and carbonate weathering, respectively, which are almost half the values of previous estimates. Our results suggest that seasonally and spatially separated evaluations are important for generating estimates of chemical weathering in large Himalayan rivers.