As one of the most important greenhouse gases, CO2 is considered a major controlling factor of Earth's climate over geological timescales. However, the origins of quasi-periodic fluctuations in pCO2 on a million-year timescale remain unclear. Here, we used published datasets of atmospheric pCO2, oxygen isotopes of benthic foraminifera (δ18Obenthic) and global mean sea-level (GMSL) from 23 Ma to the present to explore the pacing of pCO2 changes and concomitant climatic effects using multiple time series analysis approaches. Our results indicate that the evolution of late Cenozoic pCO2 and climate was paced by the grand orbital cycles, in particular the ∼4.5 Myr and ∼2.4 Myr eccentricity cycles, and ∼1.3 Myr obliquity cycle. Periodic occurrence of cold conditions was associated with low climate seasonality during the minima of ∼4.5 Myr and ∼2.4 Myr eccentricity cycles. We suggest that cooler conditions are associated with decreased atmospheric pCO2 as a result of higher organic carbon burial due to lower metabolic rate of heterotrophic bacteria and more organic carbon export to the deep ocean. Furthermore, the buildup of glaciers during the minima of grand eccentricity cycles might lower pCO2 via increased ice cover and enhanced dust fluxes. In contrast, high seasonal climate may lead to an opposite effect on atmospheric pCO2 during the maxima of the grand eccentricity cycles. Moreover, we found a distinct shift in the dominant signal from eccentricity to obliquity cycles recorded in the pCO2, δ18Obenthic and GMSL datasets at ∼13 Ma, a time when perennial sea ice occurred in the Arctic and significant ice growth shown in Antarctica. We suggest that the change in the type and distribution of the ice sheets would shift glacial response to orbital forcing and hence mediated global climate and pCO2. Our analysis reveals a clear synchrony among atmospheric pCO2, climate change, and the grand orbital cycles in the late Cenozoic.