Systematic studies of microsolvation in the gas phase have enriched our knowledge of solvent effects. Here, the dynamics of a prototype S_N2 reaction of a hydrated fluoride ion with methyl iodide is uncovered employing direct dynamics simulations that show strikingly distinct features from those determined for an unsolvated system. An indirect scattering is found to prevail, which occurs dominantly by forming hydrated F⁻(H₂O)–HCH₂I and F⁻(H₂O)–CH₃I pre-reaction complexes at low energies, but proceeds through their water-free counterparts at higher energies. This finding is in strong contrast to a general evolution from indirect to direct dynamics with enhancing energy for the unsolvated substitution reactions, and this discrepancy is understood by the substantial steric hindrance introduced by a water molecule. As established in experiments, solvation suppresses the reactivity, whereas we find that this depression is remarkably frustrated upon raising the energy given that collision-induced dehydration essentially diminishes the water block for reactive collisions. The present study sheds light on how solute–solvent interactions affect the underlying dynamics at a deeper atomic level, thereby promoting our understanding of the fundamental solvent effects on chemical reactions in solution.