In this study, we evaluate the evolution of the interfacial processes in metallic sliding contacts (i.e., aluminum alloys) in terms of their elemental composition, structural changes, and nanomechanical properties in order to understand the optimal running-in behavior leading to steady-state low friction and high wear resistance. Two different sliding conditions are used, resulting in low and high long-term friction and corresponding well with the low and high wear rates. Ex situ elemental analysis of these sliding experiments was performed by means of X-ray photoelectron spectroscopy. The mechanical properties were evaluated using nanoindentation and microcompression testing. While the elemental analysis revealed an increased oxide content for the near-surface region of the worn surfaces compared to the unworn material, the oxide content was higher for the experiments that resulted in an unfavorable tribological response (i.e., high friction and high wear). Similarly, the sub-surface grain-refined layer under these conditions was thicker compared to the experiment with a short running-in stage and low steady-state friction and wear. These observations correlated well with the nanoindentation and microcompression results, which show higher hardness and yield stress for the high friction and wear experiment. Correspondingly, low steady-state friction and wear were obtained with the formation of a thin and mechanically stable tribolayer.