Coccolithophores, a group of unicellular calcifying phytoplankton, have been major contributors to marine carbonate production since the calcite plates that they produce (coccoliths) first appeared in the fossil record over 200 million years ago (Ma). The response of this process to changes in environment on evolutionary timescales remains poorly understood, particularly in warm climates. Here we integrate a dataset consisting of carbon isotope ratios of size-separated coccolith calcite from marine sediments with a cell-scale model to interrogate cellular carbon fluxes and \(p_{{\mathrm{CO}}_2}\) through the Eocene (~55–34 Ma), Earth’s hottest interval of the past 100 million years. We show that the large coccolithophores that rose to dominate the oceans through the Eocene have higher calcification-to-carbon fixation ratios than their predecessors while the opposite is true for smaller coccolithophores. These changes, which occurred in the context of increasing ocean alkalization, may have played a role in an apparent positive carbon cycle feedback to decreasing \(p_{{\mathrm{CO}}_2}\). Our approach also provides independent support of multiproxy-based evidence for general \(p_{{\mathrm{CO}}_2}\) decline through the Eocene in step with temperature. Together, this challenges the emerging view that a general decline in \(p_{{\mathrm{CO}}_2}\) reduces calcification on evolutionary timescales.