Surface engineering and doping of zinc oxide (ZnO) nanoparticles have been two feasible techniques for improving the gas-detecting capability of these nanoparticles. However, the role of fundamental processes and factors that affect this improvement has not been fully understood. In this study, the adsorption of CO gas molecules on Pd- and Al-doped ZnO nanotubes was investigated using the first-principles calculations. The binding strength and charge transport and structural properties of these nanotubes, were studied. The CO gas molecule was strongly chemisorbed onto the Pd- and Al-doped ZnO nanotubes with a high adsorption energy of −1.36 and -1.21 eV, respectively. Finally, in order to further understand the interaction between CO gas molecule and Pd- and Al-doped ZnO nanotubes, the density of states (DOS) and the partial density of states (PDOS) of Pd- and Al-doped ZnO nanotubes before and after CO adsorption were investigated. The results provided a better atomistic insight and a more comprehensive explanation of the improvements in electrical properties and sensing capabilities of Pd- and Al-doped ZnO.