Clustering phenomena are common in many physical systems across multiple scales. The nuclear α decay is one of the earliest observed evidences of clustering in quantum systems, yet its formation process remains poorly understood even today. In this paper, we propose a novel global odd-even staggering (OES) feature in α decay, which emerges during the clustering process. To unveil its origin, we develop a universal four-fermion formation framework (U4F), which describes the formation of any four-nucleon cluster, such as α particle, from a general microscopic wave function, without assuming the preexistence of clustering or pairing. By combining U4F with the large-scale configuration-interaction approach, we demonstrate that the OES effect in α decay arises from the suppression of clustering correlations due to unpaired nucleons. These findings significantly advance our understanding of cluster formation in nuclei and have important implications for the production of new elements and nuclear synthesis in the universe.