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Water is one of the most fundamental molecules in chemistry, biology and astrophysics. It exists as two distinct nuclear-spin isomers, para- and ortho-water, which do not interconvert in isolated molecules. The experimental challenges in preparing pure samples of the two isomers have thus far precluded a characterization of their individual chemical behavior. Capitalizing on recent advances in the electrostatic deflection of polar molecules, we separate the ground states of para- and ortho-water in a molecular beam to show that the two isomers exhibit different reactivities in a prototypical reaction with trapped diazenylium ions. Based on ab initio calculations and a modelling of the reaction kinetics using rotationally adiabatic capture theory, we rationalize this finding in terms of different rotational averaging of ion-dipole interactions during the reaction.