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The Middle Miocene (~16–11.6 Ma) had atmospheric CO 2 levels comparable to the present day, and thus the mechanisms controlling the interactions of the climate system and the carbon cycle during the Middle Miocene may have significant implications for future climate change. In this study, we examined the phase relationship between benthic foraminiferal δ18O and δ13C records, within the 100-kyr band, during the Late Quaternary and the Middle Miocene. Our results suggest that benthic foraminiferal δ18O and δ13C were highly coherent and in-phase within the 100-kyr band during the Middle Miocene, in contrast to the anti-phased relationship during the Late Quaternary. However, the causes of this contrast remain elusive. We used a biogeochemical box model to explore the mechanisms of the in-phase relationship in the 100-kyr band during the Middle Miocene. The model results show that the in-phase relationship can be attributed to two mechanisms: (1) a shelf-basin carbonate shift regulated by sea-level fluctuations which originated from the growth and decay of the Antarctic ice sheet, within the 100-kyr band; and (2) changes in terrestrial carbon inputs and the biological pump driven by the discharge of riverine nutrients, which was regulated by precipitation variability in low latitudes, within the eccentricity-modulated precessional band. Thus, we propose that both high- and low-latitude processes played critical roles in the Middle Miocene carbon cycle, within the 100-kyr band. We further show that chemical weathering played a potential role in regulating the atmospheric p CO 2 on the orbital time scale during the Middle Miocene. • Phase relationships between benthic δ18O and δ13C records in the 100-kyr band are reinvestigated. • Terrestrial inputs explain the in-phase relationship of benthic δ18O and δ13C in the 100-kyr band over the Middle Miocene. • Both changes of Antarctic ice sheet and low-latitude precipitation played critical roles in the Middle Miocene carbon cycle. [ABSTRACT FROM AUTHOR]