The mechanism of the residual stress relaxation during the fatigue life of shot peened high-strength aluminum alloys was investigated. Experiments were conducted on specimens subjected to three different shot peening treatments and tested under reverse bending fatigue. x-ray diffraction (XRD) measurements were carried out to determine the initial and stabilized residual stress fields. The residual stress field created by the surface treatments has been introduced into a finite element (FE) model by means of a fictitious temperature distribution. The elastic-plastic response of the superficial layers affected by the shot peening treatments has been derived through reverse strain axial testing combined with microhardness tests and implemented in the FE model. The proposed numerical/experimental approach is able to satisfactorily predict the residual stress field evolution. Notably, relaxation has been correctly simulated in the low-cycle fatigue regime and imputed to plastic flow in compression when the superposition of compressive residual and bending stresses exceeds the local cyclic yield strength of the material. Conversely, the residual stress field remains stable at load levels corresponding to the fatigue endurance.