The high-temperature reaction pathways of bio-oil oxidation were investigated by simulations of a 24-component bio-oil model using reactive force field (ReaxFF) molecular dynamics. Evolution profiles of fuel, O-2, and major products, including radicals, with time and temperature during the initial stage of bio-oil oxidation were obtained. Major products generated during the simulations are consistent with observations reported in the literature. A kinetic model obtained from the simulated bio-oil oxidation is able to, predict a long-time evolution trend of fuel consumption. Reaction networks of five representative components of the bio-oil model were revealed. The bio-oil oxidation is initiated by a series of homolysis and H-abstraction reactions and then propagation reactions involving H-shift, H-abstraction, and beta-scission reactions. Oxidation of the unsaturated C-C bond, ring reduction of the phenolic radical, and abscission of the -CO structure (decarbonylation) appear frequently. Reaction pathways obtained from the comprehensive observations of simulation results employing VARxMD are in broad agreement with the literature. This work demonstrated a methodology that ReaxFF molecular dynamic simulations combined with the capability of VARxIVID for reaction analysis can provide useful insights into the reaction pathway of bio-oil combustion.