A novel solvent-directed click reaction between active methylene compounds and azido-1,3,5-triazines has been developed. In aqueous solution, the regiospecific trisubstituted 1,2,3-triazole products are quickly synthesized in high yields under mild conditions and easy to separate without column chromatography. This click reaction is controlled by the protonation of a nitrogen anion intermediate, and the postulated mechanism is substantiated by DFT calculations.