With regard to the physical absorbents for CO2 removal, the alteration of carbon-chain structure may benefit the CO2 absorption performance. However, the relationship between the carbon-chain structure of ketones absorbents and their CO2 absorption capacity has rarely been studied, and the related mechanism is unclear. In this study, theoretical calculations and thermodynamic experiments were carried out to explore the effects of the carbon-chain length and isomerism of ketones on their CO2 absorption performance. The density functional theory (DFT) simulations show that the F-∥ configuration is more stable than the others for the CO2+ketone complex in most cases. The followings are obtained according to the experimental results, which are pretty consistent with DFT calculations. The dissolution of CO2 in the ketone is a typical physical process. As the number of carbon atom increases, the CO2 absorption capacity of straight-chain ketones increases. Straight-chain ketones exhibit higher CO2 absorption capacity than branched-chain ones. The effect of increasing carbon-chain length and isomerism on CO2 absorption capacity are both stronger for the ketones with fewer carbon atoms; the influence mechanism can be attributed to different degrees of weak hydrogen-bond interaction between CO2 and ketone molecules, suggested by the DFT simulation results. The above conclusions are beneficial for the development of potential CO2 capture absorbents. In addition, the industrial application feasibility of surveyed ketone absorbents is also discussed.