AbstractThe Middle Eocene Climatic Optimum (MECO) represents a ~500-kyr period of global warming ~40 million years ago and is associated with a rise in atmospheric CO₂ concentrations, but the cause of this CO₂ rise remains enigmatic. Here we show, based on osmium isotope ratios (¹⁸⁷Os/¹⁸⁸Os) of marine sediments and published records of the carbonate compensation depth (CCD), that the continental silicate weathering response to the inferred CO₂ rise and warming was strongly diminished during the MECO—in contrast to expectations from the silicate weathering thermostat hypothesis. We surmise that global early and middle Eocene warmth gradually diminished the weatherability of continental rocks and hence the strength of the silicate weathering feedback, allowing for the prolonged accumulation of volcanic CO₂ in the oceans and atmosphere during the MECO. These results are supported by carbon cycle modeling simulations, which highlight the fundamental importance of a variable weathering feedback strength in climate and carbon cycle interactions in Earth’s history.