Refill friction stir spot welding (RFSSW) is an emerging technology for joining aerospace aluminum alloys. The aim of the study is to investigate the effects of the refill friction stir spot weld spacing and the edge margin on the mechanical properties of multi-spot-welded AA7075-T6 panels. AA7075-T6 is a baseline aerospace aluminum alloy used in aircraft structures. The study employs an innovative robotic RFSSW system that is designed and developed by Kawasaki Heavy Industries (KHI). The experimental strategy uses Design of Experiments (DoE) to characterize the failure loads of multi-spot-welded panels in terms of the spot weld spacing, edge margin, and heat-affected zone (HAZ) of the spot weld. The RFSSW process leaves behind a thermal “imprint” as HAZ in heat-treatable aluminum alloys. According to the DoE results, larger spot weld spacings with no HAZ overlap produce higher failure loads of multi-spot-welded panels. On the other hand, edge margins that are equal to or less than the spot weld diameter demonstrate abnormal plastic deformations, such as workpiece edge swelling and weld crown dents, during the RFSSW process. The larger edge margins do not demonstrate such abnormal deformations during the welding process.