The CaO and Fe(III)/CaO catalysts were prepared and employed for catalytic upgrading of biomass fast pyrolysis vapors by pyrolysis-gas chromatography/mass spectrometry instrument (Py-GC/MS). It was found that the Fe(III)/CaO catalyst was effective in upgrading the biomass fast pyrolysis vapors by reducing the amount of oxygenated compounds. The Fe(III)/CaO catalyst displayed good capabilities to transform the heavy phenols to light phenols without the methoxyl group and unsaturated CC bonds on the side chain. Moreover, the catalyst completely eliminated the acids and significantly decreased the yields of aldehydes and ketones. The yields of furans, light and aromatic hydrocarbons were greatly increased. Based on the results of catalyst characterization and activity experiments, it seems that the higher activity of the Fe(III)/CaO catalyst is related to the synergistic effect between Fe and CaO support, and the Ca2Fe2O5 phase formed in the catalyst might protect the CaO support and inhibit the Fe sintering in the upgrading reactions.