<p>Ocean alkalinity enhancement is a widely considered approach for marine CO₂ removal. Alkalinity enhancement sequesters atmospheric CO₂ by shifting the seawater carbonate equilibrium from CO₂ towards bicarbonate and carbonate ions. Such re-equilibration has been hypothesized to benefit calcifying organisms, whose increased calcification could strongly reduce the efficiency of alkalinity enhancement. Here we use global ocean satellite data to constrain the sensitivity of coccolithophores—an important group of calcifying phytoplankton—to natural gradients of seawater carbonate chemistry. We show that the ratio of particulate inorganic to particulate organic carbon, reflecting the balance of calcifying versus non-calcifying phytoplankton, is influenced by environmental drivers, including nutrient stoichiometry and carbon substrate within biogeochemical provinces. Across biogeochemical provinces, however, this ratio persistently correlates with carbonate chemistry through combined influences of carbon substrate availability and proton inhibition of calcification. We estimate that extreme alkalinity enhancement may promote the proliferation of coccolithophores, thereby reducing the CO₂ removal potential of ocean alkalinity enhancement by 2–29% by 2100. However, less extreme alkalinity enhancement may only mitigate for adverse acidification effects on coccolithophores. Our findings demonstrate the importance of considering large-scale biogeochemical feedbacks when evaluating the efficiency of ocean alkalinity enhancement.</p>