It remains unclear whether waning of the volcanic degassing CO2 source or enhancement of the mafic (Ca, Mg-silicate) weathering CO2 sink, or both, caused global cooling leading to the Ordovician greenhouse–icehouse transition. We present a uniquely age-constrained and integrated Middle–Late Ordovician (470–450 Ma) continental weathering isotopic proxy data set (87Sr/86Sr and εNd(t)) from carbonate rocks of the Antelope Range of central Nevada, USA, paired with published paleotemperature proxy measurements (δ18O) of conodont apatite from the same locality. This suite of proxy records signals an increase in mafic weathering of the Taconic mountains (eastern United States) at ca. 463 Ma, which forced a period of global cooling. We adapt a 87Sr/86Sr and pCO2 mass balance approach to model CO2 drawdown during the Ordovician, and show that a combined decrease in volcanic degassing and increase in mafic weathering approximately halves pCO2 in agreement with δ18O trends and paleotemperature reconstructions.