Using methylene blue (MB) as a model system, we demonstrate surface plasmon-enhanced resonant excitation that leads to N-demethylation reaction under visible light irradiation (λ = 633 nm) at low photon flux. The chemical changes are monitored by detecting the vibrational signatures of the reactant and product species in situ using surface-enhanced Raman scattering (SERS) spectroscopy. Drastic temporal evolution of SERS spectra has been observed upon continuous irradiation. While the SERS spectra acquired immediately after irradiation are the same as the Raman spectrum of MB solid powder, the spectra recorded a few seconds later are remarkably similar to that of thionine solid powder, indicating N-demethylation of MB. No demethylation reaction has been observed under resonant excitation (λ = 633 nm) of MB adsorbed on nonplasmonic surfaces. Similarly, excitations of plasmon resonances at 532 and 808 nm wavelengths that do not overlap with the MB electronic transition do not lead to transformation of MB to thionine. The reaction mechanism is discussed in terms of resonant excitation of MB and hot electron transfer to adsorbed species. Considering that both MB and thionine have large SERS signal due to the combination of resonance Raman and electromagnetic enhancement effects that provide high detection sensitivity, we suggest that this demethylation reaction serves as a convenient model system for future mechanistic studies.