Despite the ever-increasing attention given to the global environmental issues caused by polymer material waste, the development of biodegradable yet mechanically reliable rubber materials remains an ongoing challenge. In this study, we developed mechanically robust polyisoprene (PI) rubber with biodegradability in seawater via the use of a water-responsive boronate ester as a dynamic cross-link. Linear PIs with varying molecular weights were derived from natural rubber through metathetic degradation, and their marine biodegradability was studied. The marine biodegradability of the PI progressively increased as the molecular weight decreased. With this knowledge in hand, we proceeded with chain-end modification of low-molecular-weight PI with boronic acid, which could form a hydrolyzable boronate ester (BE) with tannic acid, a naturally occurring polyphenol. Compared with conventional permanently cross-linked PI rubber, which did not show discernible biodegradation, the BE cross-linked PI rubber showed significant biodegradability in an inoculum derived from natural seawater (40–50% mineralization to CO2 and H2O in 4 months) while demonstrating comparable mechanical robustness (stress at break = 2.5–3.7 MPa, strain at break = 290–420%, and Young’s modulus = ca. 1.0 MPa in the dry state). This work presents for the first time the possibility of biodegradable yet robust cross-linked rubber that contributes to the realization of a sustainable society.