Abstract The Piacenzian stage of the Pliocene (2.6 to 3.6 Ma) is the most recent past interval of sustained global warmth with mean global temperatures markedly higher (by ~2–3 °C) than today. Quantifying CO 2 levels during the mid-Piacenzian Warm Period (mPWP) provides a means, therefore, to deepen our understanding of Earth System behaviour in a warm climate state. Here we present a new high-resolution record of atmospheric CO 2 using the δ 11 B-pH proxy from 3.35 to 3.15 million years ago (Ma) at a temporal resolution of 1 sample per 3–6 thousand years (kyrs). Our study interval covers both the coolest marine isotope stage of the mPWP, M2 (~3.3 Ma) and the transition into its warmest phase including interglacial KM5c (centered on ~3.205 Ma) which has a similar orbital configuration to present. We find that CO 2 ranged from $${{\bf{394}}}_{{\boldsymbol{-}}{\bf{9}}}^{{\boldsymbol{+}}{\bf{34}}}$$ 394 − 9 + 34 ppm to $${{\bf{330}}}_{{\boldsymbol{-}}{\bf{21}}}^{{\boldsymbol{+}}{\bf{14}}}$$ 330 − 21 + 14 ppm: with CO 2 during the KM5c interglacial being $${{\bf{391}}}_{{\boldsymbol{-}}{\bf{28}}}^{{\boldsymbol{+}}{\bf{30}}}$$ 391 − 28 + 30 ppm (at 95% confidence). Our findings corroborate the idea that changes in atmospheric CO 2 levels played a distinct role in climate variability during the mPWP. They also facilitate ongoing data-model comparisons and suggest that, at present rates of human emissions, there will be more CO 2 in Earth’s atmosphere by 2025 than at any time in at least the last 3.3 million years.