Guaiacol (2-methoxyphenol) and its derivatives are a class of semivolatile polar organic molecules possessing low molecular weights. Owing to their volatility, guaiacol and its derivatives can interact with atmospheric water and form protonated methoxyphenols through proton transfer. The aim of the present work is to study the dissociation of these protonated ions and hence, potentially, their atmospheric fate. Tandem mass spectrometry was employed to analyze the unimolecular dissociation of the protonated forms of guaiacol (2-methoxyphenol, 1), creosol (2-methoxy-4-methylphenol, 2), 4-ethylguaiacol (4-ethyl-2-methoxyphenol, 3), 4-vinylguaiacol (2-methoxy-4-vinylphenol, 4), eugenol (2-methoxy-4-prop-2-enylphenol, 5), and vanillin (4-hydroxy-3-methoxybenzaldehyde, 6). Density functional theory at the B3LYP/6-31G(d) (1-5) and B3LYP/6-311+G(d,p) (6) levels of theory were applied to determine the observed minimum energy reaction pathways, and reliable energetics were acquired using CBS-QB3 single-point energy calculations. All the protonated ions, with the exception of 6, exhibit the loss of CH3OH via a series of hydrogen transfers, followed by ring contraction to lose CO. This common dissociation pathway leads to the formation of a cyclopentadienyl ion as the main dissociation product. Conversely, 6 first exhibits the loss of CO, followed by sequential losses of CH3OH and CO to generate a cyclopentadienyl ion. Additionally, minor fragmentation channels are also observed for the different protonated ions: CH2 loss in 1; CH4 and H2O losses in 3; CH3 loss in 4, 5, and 6; C2H4 and CH2CHCH2 losses in 5; H loss in 6. Altogether, the protonated ions primarily lose CH3OH and CO as neutral molecules and generate a cyclopentadienyl ion as a dissociation product.