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A cooling trend during the Middle Ordovician may have resulted in significant biotic, atmospheric and hydrologic changes, but the exact timing and forcing of this climate event still remain largely ambiguous. Here, we present astronomically calibrated magnetic susceptibility (MS) and gamma ray (GR) data from the shale and carbonate successions of the Kalpin area in the Tarim Basin, NW China to study the Middle Ordovician climate. The spectral analyses of the 405-kyr calibrated MS and GR time series reveal periodicities close to 405 (calibrated), 100, 31 and 19 kyr, supporting a Milankovitch forcing for the sedimentary cyclicity. The eccentricity and obliquity amplitude modulation cycles show main periodicities of similar to 2.4 and similar to 1.2 Myr, respectively. A cooling event along with the middle Darriwilian isotope carbon excursion (MDICE) appears to have been initiated by the alignment of the eccentricity and obliquity amplitude minima at 4.07 Myr prior to the Darriwilian/Sandbian (D/S) boundary. This climate event was in pace with high-amplitude obliquity oscillations during a period when the 1.2 Myr obliquity amplitude modulation cycles controlled the global third-order eustatic sequences. The termination of this cooling event corresponding to a global third-order highstand was initiated by an eccentricity oscillation maximum at 0.63 Myr prior to the D/S boundary. Subsequent climate alleviation was dominated by eccentricity forcing until the earliest Sandbian. We suggest that although the climate changes have been primarily associated with the CO2 level, a specific sequence of astronomical variations during the Middle Ordovician was responsible for the time when the critical threshold was crossed.