The Southern Ocean is one of the most pristine environments in the world, but is nonetheless affected by inputs of persistent organic pollutants (POPs). In the present work, we report the concentrations of hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), and 26 polychlorinated biphenyl (PCBs) congeners in seawater and phytoplankton from samples obtained during three Antarctic cruises in 2005, 2008, and 2009. The levels of PCBs, HCHs, and HCB are low in comparison to the few previous reports for this region and studies from other oceans. The long-term decline of POP concentrations in the Southern Ocean seawater since early 1980 is consistent with half-lives of 3.4 and 5.7 years for HCHs and PCBs, respectively. There is a large variability of PCBs, HCHs, and HCB concentrations in water and phytoplankton within the Bransfield Strait, South Scotia, Weddell, and Bellingshausen Seas that masks the differences between the studied Seas. However, the variability of PCBs concentrations in phytoplankton is significantly correlated with phytoplankton biomass, with lower concentrations in the most productive waters. This trend is more apparent for the more hydrophobic congeners, consistent with the role of settling fluxes of organic matter decreasing the concentrations of hydrophobic POPs in productive waters. The present work reports the most extensive data set on concentrations in seawater and phytoplankton for the Southern Ocean, and points to the important biogeochemical drivers, such as settling and degradation, influencing the occurrence of POPs in the ocean.