ABSTRACT Anthropogenic CO 2 emissions are projected to lower the pH of the open ocean by 0.2 to 0.3 units over the next century. Laboratory experiments show that different phytoplankton taxa exhibit a wide variety of responses, with some strains having higher fitness under projected future conditions, and others being negatively impacted. Previous studies have suggested that Prochlorococcus and Synechococcus , the numerically dominant picophytoplankton in the oceans, have very different responses to elevated CO 2 that may result in a dramatic shift in their relative abundances in future oceans. Here we show that these two genera experience faster exponential growth rates under future CO 2 conditions, similar to most other cyanobacteria that have been studied. However, Prochlorococcus strains have significantly lower realized growth rates due to more extreme lag periods after exposure to fresh culture media. Surprisingly, however, Synechococcus was unable to outcompete Prochlorococcus in co-culture at elevated CO 2 . Under these conditions, Prochlorococcus ’ poor response to elevated CO 2 disappeared, and it showed negative frequency dependence in its relative fitness compared to Synechococcus , with a significant fitness advantage when it was initially rare. Moreover, both Synechococcus and Prochlorococcus had faster growth rates in co-culture with each other than either had in unialgal culture. We speculate that this negative frequency dependence is an outgrowth of reductive Black Queen evolution operating on both taxa that has resulted in a passively mutualistic relationship analogous to that connecting Prochlorococcus with the “helper” heterotrophic microbes in its environment.