The long-term reliability of flexible electronics depends on the durability of metallic interconnects. Fatigue failure in these interconnects is driven by two mechanisms: crack initiation from surface extrusions and delamination at the metal/polymer interface. Here, we propose a Cu-Mn alloy interconnect that utilizes a self-forming nanolayer to simultaneously address both failure modes. Through postannealing of a vapor-deposited Cu-Mn film, manganese diffuses to form an similar to 20 nm thick manganese oxide (MnOx) layer at both the surface and the interface. This surface MnOx layer effectively suppresses extrusions, the primary sites for fatigue cracks. Concurrently, the interfacial MnOx layer enhances adhesion energy to 10.77 J/m2, a similar to 2.2-fold improvement over annealed pure Cu, thus preventing delamination. As a result, the Cu-Mn interconnects exhibit a significant enhancement in fatigue lifetime, confirming the dual role of MnOx in improving both surface stability and interfacial integrity. This work provides a unified and experimentally validated strategy for improving the reliability of flexible electronic interconnects.