Poly(butylene succinate) (PBSu) is a promising biodegradable polymer in natural environments. However, its biodegradability in marine environments is debatable. It is well known that the biodegradability of biodegradable polymers depends on their molecular weight. In this study, we explored the effect of the molecular weight of PBSu on its biodegradability through biochemical oxygen demand (BOD) testing in seawater. PBSu samples with different molecular weights were prepared by size-exclusion chromatography (SEC). After biodegradation testing, we extracted the residual organic matter from seawater to evaluate changes in the molecular weight by SEC, revealing that PBSu was enzymatically hydrolysed in seawater. Low-molecular-weight (LMW)-PBSu exhibited higher biodegradability in seawater while high-molecular-weight PBSu underwent hydrolysis over an extended period. Moreover, we evaluated the changes in microbial flora during biodegradation testing using amplicon sequencing of the culture media, which revealed that the microbial flora changed in response to the presence of PBSu. These findings suggest that PBSu is a potential biodegradable polymer at a sufficiently low molecular weight or when the degradation period is sufficiently long.