Stratospheric ozone depletion plays a major role in driving climate change in the Southern Hemisphere. To date, many climate models prescribe the stratospheric ozone layer’s evolution using monthly and zonally averaged ozone fields. However, the prescribed ozone underestimates Antarctic ozone depletion and lacks zonal asymmetries. This study investigates the impact of using interactive stratospheric chemistry instead of prescribed ozone on climate change simulations of the Antarctic and Southern Ocean. Two sets of 1960–2010 ensemble transient simulations are conducted with the coupled ocean version of the Goddard Earth Observing System Model, version 5: one with interactive stratospheric chemistry and the other with prescribed ozone derived from the same interactive simulations. The model’s climatology is evaluated using observations and reanalysis. Comparison of the 1979–2010 climate trends between these two simulations reveals that interactive chemistry has important effects on climate change not only in the Antarctic stratosphere, troposphere, and surface, but also in the Southern Ocean and Antarctic sea ice. Interactive chemistry causes stronger Antarctic lower stratosphere cooling and circumpolar westerly acceleration during November– January. It enhances stratosphere–troposphere coupling and leads to significantly larger tropospheric and surface westerly changes. The significantly stronger surface wind stress trends cause larger increases of the Southern Ocean meridional overturning circulation, leading to year-round stronger ocean warming near the surface and enhanced Antarctic sea ice decrease.