Abstract The amplitude of climatic change, as recorded in the benthic oxygen isotope record, has varied throughout geological time. During the late Pleistocene, changes in the atmospheric concentration of carbon dioxide (CO 2 ) are an important control on this amplitude of variability. The contribution of CO 2 to climate variability during the pre‐Quaternary however is unknown. Here we present a new boron isotope‐based CO 2 record for the transition into the middle Miocene Climatic Optimum (MCO) between 15.5 and 17 Myr that shows pronounced variability between 300 ppm and 500 ppm on a roughly 100 kyr time scale during the MCO. The CO 2 changes reconstructed for the Miocene are ~2 times larger in absolute terms (300 to 500 ppm compared to 180 to 280 ppm) than those associated with the late Pleistocene and ~15% larger in terms of climate forcing. In contrast, however, variability in the contemporaneous benthic oxygen isotope record (at ~1‰) is approximately two thirds the amplitude of that seen during the late Pleistocene. These observations indicate a lower overall sensitivity to CO 2 forcing for Miocene (Antarctic only) ice sheets than their late Pleistocene (Antarctic plus lower latitude northern hemisphere) counterparts. When our Miocene CO 2 record is compared to the estimated changes in contemporaneous δ 18 O sw (ice volume), they point to the existence of two reservoirs of ice on Antarctica. One of these reservoirs appears stable, while a second reservoir shows a level of dynamism that contradicts the results of coupled climate‐ice sheet model experiments given the CO 2 concentrations that we reconstruct. Key Points The middle Miocene is characterized by CO 2 variability between 300 and 500 ppm The high‐amplitude CO 2 variability is matched by the changes in the paleorecords Two regimes of ice volume‐CO 2 variability identified in middle Miocene