We studied the valence photoionization of vanillin by photoelectron photoion coincidence spectroscopy in the 8.20–19.80 eV photon energy range. Vertical ionization energies by EOM-IP-CCSD calculations reproduce the photoelectron spectral features. Composite method calculations and Franck-Condon simulation of the weak, ground-state band yield the adiabatic ionization energy of the most stable vanillin conformer as 8.306(20) eV. The lowest energy dissociative photoionization channels correspond to hydrogen atom, carbon monoxide, and methyl losses, which form the dominant C₈H₇O₃⁺ (m/z 151) and the less intense C₇H₈O₂⁺ (m/z 124) and C₇H₅O₃⁺ (m/z 137) fragment ions in parallel dissociation channels at modeled 0 K appearance energies of 10.13(1), 10.40(3), and 10.58(10) eV, respectively. On the basis of the breakdown diagram, we explore the energetics of sequential methyl and carbon monoxide loss channels, which dominate the fragmentation mechanism at higher photon energies. The 0 K appearance energy for sequential CO loss from the m/z 151 fragment to C₇H₇O₂⁺ (m/z 123) is 12.99(10) eV, and for sequential CH₃ loss from the m/z 123 fragment to C₆H₄O₂⁺ (m/z 108), it is 15.40(20) eV based on the model. Finally, we review the thermochemistry of the bi- and trifunctionalized benzene derivatives guaiacol, hydroxybenzaldehyde, anisaldehyde, and vanillin. On the basis of isodesmic functional group exchange reactions, we propose new enthalpies of formations, among them Δ_fH°_298K(vanillin, g) = -383.5 ± 2.9 kJ mol^-1. These mechanistic insights and ab initio thermochemistry results will support analytical works to study lignin conversion involving vanillin.