The Osumi Granodiorite, located on the Osumi Peninsula in southwest Japan, is an example of outer zone granites that were formed during a limited period (13–15 Ma) in response to the subduction of the Philippine Sea Plate. This event, which is linked to the separation of southwest Japan from continental Asia, resulted in unique igneous activity. The Osumi Granodiorite is the largest Miocene granite body in the region. It intrudes into the Mesozoic to Paleogene accretionary complex of the Shimanto Belt and affects contact metamorphism. Despite considerable research on the Osumi Granodiorite, limited geochemical studies, especially on trace and rare earth element (REE) analyses, have been conducted. Furthermore, there are insufficient data on the Rb–Sr isotopic system, leaving the formation process unclear. This study presents whole-rock geochemical and Rb-Sr isotopic data to investigate the petrogenesis of the Osumi Granodiorite. The results suggest a common magma origin for this pluton, as indicated by linear trends on the Harker diagrams and similar REE patterns. The presence of a relatively large Eu anomaly implies formation under a reducing environment. The AKF diagram indicates predominant contamination by pelitic rocks of the Shimanto Belt during magma formation. The Rb–Sr whole-rock isochron diagram and SrI–1000/Sr diagram suggest that the Osumi Granodiorite body was formed by heterogeneous assimilation of magma into the Shimanto Belt. Furthermore, the whole-rock isochron age is 64.3 Ma, which differs by approximately 50 My from the previously reported biotite K–Ar age (14–22 Ma). This age is considered to be a pseudo-isochron age, rather than the consolidation age. During the middle Miocene, the compressive stress field in the outer zone south of the Butsuzo Tectonic Line made it difficult for magma to rise. As a result, it reacted with the sedimentary rocks of the Shimanto Belt to various degrees. The Osumi Granodiorite underwent magma differentiation upon intrusion into the Shimanto Belt. It subsequently ascended, cooled, and interacted with pelitic rocks under stable geological conditions.