The chemistry of methanol was explored on the vacuum annealed TiO₂(110) surface, with and without the presence of coadsorbed water and oxygen, using temperature programmed desorption (TPD), high resolution electron energy loss spectroscopy (HREELS), static secondary ion mass spectrometry (SSIMS) and low energy electron diffraction (LEED). The vacuum annealed TiO₂(110) surface possessed about 8% oxygen vacancy sites, as determined with H₂O TPD. Although evidence is presented for CH₃OH dissociation to methoxy groups on the vacuum annealed TiO₂(110) surface using SSIMS and HREELS, particularly at vacancy sites, the majority of the adlayer was molecularly adsorbed, evolving in TPD at 295 K. Although no evidence of irreversible decomposition was found in the TPD, dissociative CH₃OH adsorption at 135 K on the vacuum annealed TiO₂(110) surface led to recombinative desorption states at 350 and 480 K corresponding to methoxys adsorbed at non-vacancy and vacancy sites, respectively. Coadsorbed water had little or no influence on the chemistry of CH₃OH on the vacuum annealed TiO₂(110) surface, however new channels of chemistry were observed when CH₃OH was adsorbed on the surface after O₂ adsorption at various temperatures. In particular, O₂ exposure at 300 K resulted in O adatoms (via dissociation at vacancies) that led to increased levels of CH₃O–H bond cleavage. The higher surface coverage of methoxy then resulted in a disproportionation reaction to form CH₃OH and H₂CO above 600 K. In contrast, low temperature exposure of the vacuum annealed TiO₂(110) surface to O₂ resulted in low temperature state of O₂ (presumably an O₂^- species) that oxidized CH₃OH to H₂CO by C–H bond cleavage. These results provide incentive to consider alternative thermal and photochemical oxidation mechanisms that involve the interaction of organics and oxygen at surface defect sites.