Methyl butyl ketone (MBK, 2-hexanone) is a common atmospheric oxygenated volatile organic compound (OVOC) owing to broad industrial applications, but its atmospheric oxidation mechanism remains poorly understood. Herein, the detailed mechanisms and kinetic properties of MBK oxidation initiated by OH radicals and subsequent transformation of the resulting intermediates are performed by employing quantum chemical and kinetic modeling methods. The calculations show that H-abstraction at the C4 position of MBK is more favorable than those at the other positions, with the total rate coefficient of k(T) = 4.13 × 10-14 exp(1576/T) cm3 molecule-1 s-1 at 273-400 K. The dominant pathway of unimolecular degradation of the C-centered alkyl radical is 1,2-acyl group migration. For the isomerization of the peroxy radical RO2, 1,5- and 1,6-H shifts are more favorable than 1,3- and 1,4-H shifts. The multiconformer rate coefficient kMC-TST of the first H-shift of the RO2 radical is estimated to be 1.40 × 10-3 s-1 at room temperature. Compared to the H-shifts of analogous aliphatic RO2 radicals, it can be concluded that the carbonyl group enhances the H-shift rates by as much as 2-4 orders of magnitude. The rate coefficients of the RO2 radical reaction with the HO2 radical exhibit a weakly negative temperature dependence, and the pseudo-first-order rate constant k'HO2 = kHO2[HO2] is calculated to be 3.32-22.10 × 10-3 s-1 at ambient temperature. The bimolecular reaction of the RO2 radical with NO leads to the formation of 3-oxo-butanal as the main product with the formation concentration of 2.2-7.4 μg/m3 in urban areas. The predicted pseudo-first-order rate constant k'NO = kNO[NO] is 2.20-9.98 s-1 at room temperature. By comparing the kMC-TST, k'HO2, and k'NO, it can be concluded that reaction with NO is the dominant removal pathway for the RO2 radical formed from the OH-initiated oxidation of MBK. These findings are expected to deepen our understanding of the photochemical oxidation of ketones under realistic atmospheric conditions.