This study aims to investigate the interplay between waste-management strategies and their environmental impacts. We focus on a highly mobile and persistent radionuclide, iodine-129 (I-129), within spent nuclear fuel (SNF), which is the dominant risk contributor from geological disposal and at existing groundwater contamination sites. Our fuel-cycle results show that the current recycling practice releases more than 90% of I-129 into the present-day biosphere, while the direct disposal of SNF in geological repositories is likely to reduce the release by eight orders of magnitude over one million years. Release from recycling can be reduced by gaseous filters, which are then disposed of in near-surface waste repositories. In addition, our data synthesis of surface-water concentrations near four nuclear facilities shows that the dilution strategy results in lower concentrations than regulatory standards, although the concentrations are significantly higher than the background over a large area and bioaccumulation has been reported. On the other hand, insufficient waste isolation in the past has resulted in locally high concentrations within one site. Our analysis suggests that (1) it is essential to consider effluents more explicitly as a part of the waste, (2) as society moves from dilution to isolation of waste (including CO2), the potential risks of waste isolation to local regions should be carefully evaluated, and (3) excessive burdens of proof could hinder/discourage waste sequestration. Comprehensive waste management strategies—considering not just volume but also mobility, isolation technologies, and ultimate fates—are needed for persistent contaminants.