Copper nanoclusters (Cu NCs) are highly promising nanomaterials in the field of electrochemiluminescence (ECL). Nevertheless, their limited stability and efficiency have impeded their practical applications. Here, we introduced a novel supramolecular anchoring strategy resulting in the creation of exceptionally stable Cu NCs (CET-Cu NCs) with remarkable ECL properties. Specifically, CET-Cu NCs exhibited a relative ECL efficiency (ΦECL) of 62% based on the annihilation ECL efficiency of [Ru(bpy)3]2+ (100%), with tripropylamine employed as a coreactant. Moreover, CET-Cu NCs can generate ECL emission through multiple different paths, which enables them to serve as signal probes in a wider range of testing scenarios, thereby enhancing the reliability and robustness of sensing and analytical systems. To demonstrate the practical utility, CET-Cu NCs were selected as an ECL signal probe for a sensing platform that facilitated ultrasensitive detection of progesterone via oriented immobilization technology and antibody/aptamer sandwich assays. This study surmounted the barriers to the practical application of Cu NCs through the implementation of a supramolecular anchoring strategy, thereby providing enhanced utility of Cu NCs in ECL sensing and analysis.