The magnesium isotopic composition (δ26Mg) of river water could provide evidence for continental weathering and the global Mg cycle. However, constraining the lithological and isotope fractionation controls on river δ26Mg is still a challenge. Here, we investigated δ26Mg of various compartments in granitic and basaltic catchments, and δ26Mg of river water in sandstone catchments in the Southeastern Tibetan Plateau. Rivers draining sandstone have the lowest δ26Mg values (−1.86‰ to −1.42‰) due to weathering of carbonate which may exhibit as a matrix, cement morphology, and layers crystallized around silicate. The δ26Mg values of river water in granitic and basaltic catchments are −0.72‰ to −0.54‰ and −0.52‰ to −0.30‰, respectively, lower than the soil and plant in the corresponding catchments. Sequestration of isotopically heavy Mg into clays during silicate weathering is predominant and produces a fractionated source of river water with isotopically light Mg. Such Mg isotope fractionation could be affected by denudation rate which changes mineral residence time in these catchments. The strong correlations between Ca/Mg molar ratio, 1/Mg, and δ26Mg value in rivers draining silicate indicate that Mg re-distribution between secondary clays and solutions is proportional to Mg isotope fractionation, the decrease of riverine Mg from silicate weathering will be accompanied by the decrease of riverine δ26Mg. Based on this, a limited impact of Mg isotope fractionation on river δ26Mg is inferred at the continental scale.