A surprising switch of the protonated site from methanol to water in protonated methanol–water mixed clusters,H⁺(MeOH)_m(H₂O)₁ (m = 1–9), was investigated by a joint theoretical and vibrational spectroscopic study. Extensive density functional calculations on all possible structural isomers revealed that the switch of the ion core is correlated with the size dependence and structural development of the hydrogen-bond network: (1) the CH₃OH₂⁺ ion core is preferred for the small-sized clusters of m = 1 and 2, (2) coexistence of the H₃O⁺ and CH₃OH₂⁺ ion cores is highly plausible for 3 ≤ m ≤ 7 clusters, and (3) obvious preference of the H₃O⁺ ion core appears from m ≥ 8 with the appearance of the characteristic “tricyclic” structure of the hydrogen-bond network. The ion core switch at m ≈ 8 is experimentally supported by the infrared photodissociation spectra of the size-selected clusters and the size dependence of the fragmentation channel following vibrational excitation.