Open-section composite profiles are often used as columns in civil engineering structures. Their thin-walled nature makes these sections prone to buckling phenomena when loaded in compression. This paper presents a study on the axial compressive performances and failure behavior of channel-section CFRP/Al laminate columns with two different stacking sequences. Typical mechanical responses and failure characteristics were first explored through experiments. Then the damage propagation mechanisms of the two kinds of columns were further compared based on a three-dimensional progressive damage model. The results indicated that column with CFRP layers stacked on the exterior surfaces exhibited smaller delaminated areas compared with the ones with aluminum alloy layers stacked exteriorly, thus resulting in the higher load-bearing capacities. Finally, a concise theoretical calculation equation for buckling load was derived, based on which further structural parametric analysis were performed.