Variations in the efficiency of the biological pumping of carbon from the surface to the deep ocean have been invoked to explain changes in atmospheric pCO2 and thus climate on a variety of timescales. We compiled published Paleocene and Eocene foraminiferal carbon isotope data and adjusted them to a uniform timescale to investigate changes in the biological pump in the early Cenozoic. Eight basinal time series were binned into 0.01 Ma increments and five water column depth horizons. The carbon isotope data reveal remarkably coherent trends in surface, thermocline, and deep water carbon isotope values through the Paleocene and Eocene. These data were used to drive a three-box ocean carbon isotope model to estimate long-term relationships among changes in atmospheric pCO2, organic and inorganic carbon burial, and biological pumping. Our model results provide evidence for two different modes of organic carbon cycling. During the Paleocene and earliest Eocene, atmospheric pCO2 drawdown was driven externally by terrestrial organic carbon burial. After the earliest Eocene, variations in atmospheric pCO2 resulting from imbalances in organic carbon cycling appear to have been driven by variations in the biological pump. A temporary decline in biological pump efficiency at ∼50 Ma may have led to increased atmospheric pCO2, increased weathering and nutrient delivery to the oceans, and enhanced organic carbon burial. Thus, a biological-pump-driven increase in atmospheric pCO2 created a counterintuitive inverse relationship between organic carbon burial and atmospheric pCO2, with no indication of the burial event in the surface water carbon isotope record.