Ti+ is known to react with acetone (CH3COCH3) to produce TiO+ and CH2CHCH3 as products, but the detailed reaction mechanism and the most favorable reaction pathway have not yet been elucidated. Here, we investigate the doublet and quartet potential-energy surfaces associated with the gas-phase reaction between Ti+ and acetone for three plausible pathways, (i) direct metal-ion insertion into the C=O bond, (ii) direct H shift, and (iii) metal-mediated H migration, by using the density functional theory (DFT) and ab initio methods. The molecular structures of intermediates and transition states involved in these reaction pathways are optimized at the DFT level by using the PBEO functional. All transition states are identified by using the intrinsic reaction coordinate (IRC) method, and the resulting reaction coordinates describe how Ti+ activates the C=O bond of CH3COCH3 (acetone) and yields TiO+ and CH2CHCH3 (propene) as products. The intersystem crossing (ISC) point is optimized by a multireference ab initio method, and spin-orbit effects are considered around the ISC point. On the basis of the presented results, we propose that the most favorable reaction pathway proceeds via the direct metal-ion insertion into the C=O bond and passes through an ISC point.