Understanding the effect of Al doping on CO adsorption at ZnO(100) is crucial for designing a high-performance CO gas sensor. In this work, we investigated the adsorption properties of CO on pristine and Al-doped ZnO(100) by performing DFT+U calculations. It is found that the doping of Al on ZnO(100) induces the semiconductor-to-metal transition and thus enhances the conductance of the substrate. Compared to the pristine ZnO(100), the adsorption energy of CO on the Al-doped surfaces is significantly enhanced since Al doping has the effect of strengthening the adsorption bond. The bonding analysis reveals that CO adsorbs on pristine ZnO(100) via the sole σ-dative donation between the CO HOMO 5σ and the empty states of the Zn cation while π-back donation from filled states of Zn or Al cations to the CO 2π* LUMO is facilitated on the Al-doped surfaces. The π-back donation also results in the red-shift of the CO stretching frequency on the Al-doped surfaces, contrasting to the blue-shift on the pristine surface. The simulated results demonstrate that the doping of Al to a three-fold coordinated site on ZnO(100) is highly beneficial for boosting the performance of the CO gas sensor. Our theoretical investigation provides fundamental insights into the effect of Al doping on the sensing mechanism for CO at the ZnO(100) surface.