Friction spot welding is an appealing technique for joining dissimilar materials, such as aluminum and copper that have significant differences in physical and mechanical properties. To optimize the welding process, a full-factorial design was employed. It is found that in addition to the plunge depth, the interaction between the rotational speed and the plunge depth significantly influences the lap-shear strength of the Al/Cu dissimilar joints. Further investigations on macro- and microstructures show that increasing the plunge depth could deform the Cu sheet into a concave shape to form a mechanical interlocking, and thus increase the joint lap-shear strength; increasing the tool rotational speed, however, may compromise this effect because of the formed tunnel defects on the interface due to high thermal exposure.