The Miocene Climatic Optimum (MCO; ca. 17–14.7 Ma) represents one of several major interruptions in the long-term cooling trend of the past 50 m.y. To date, the processes driving high-amplitude climate variability and sustaining global warmth during this remarkable interval remain highly enigmatic. We present high-resolution benthic foraminiferal and bulk carbonate stable isotope records in an exceptional, continuous, carbonate-rich sedimentary archive (Integrated Ocean Drilling Program Site U1337, eastern equatorial Pacific Ocean), which offer a new view of climate evolution over the onset of the MCO. A sharp decline in δ18O and δ13C at ca. 16.9 Ma, contemporaneous with a massive increase in carbonate dissolution, demonstrates that abrupt warming was coupled to an intense perturbation of the carbon cycle. The rapid recovery in δ13C at ca. 16.7 Ma, ∼250 k.y. after the beginning of the MCO, marks the onset of the first carbon isotope maximum within the long-lasting “Monterey Excursion.” These results lend support to the notion that atmospheric pCO2 variations drove profound changes in the global carbon reservoir through the MCO, implying a delicate balance between changing CO2 fluxes, rates of silicate weathering, and global carbon sequestration. Comparison with a high-resolution δ13C record spanning the onset of the Cretaceous Oceanic Anoxic Event 1a (∼120 m.y. ago) reveals common forcing factors and climatic responses, providing a long-term perspective to understand climate–carbon cycle feedbacks during warmer periods of Earth’s climate with markedly different atmospheric CO2 concentrations.