Changes in atmospheric CO2 on millennial‐to‐centennial timescales are key components of past climate variability during the last glacial and deglacial periods (70‐10ka) yet the sources and mechanisms responsible for the CO2 fluctuations remain largely obscure. Here we report the 13C/12C ratio of atmospheric CO2 during a key interval of the last glacial period at sub‐millennial resolution, with coeval histories of atmospheric CO2, CH4 and N2O concentrations. The carbon isotope data suggest that the millennial‐scale CO2 variability in MIS3 is driven largely by changes in the organic carbon cycle, most likely by sequestration of respired carbon in the deep ocean. Centennial‐scale CO2 variations, distinguished by carbon isotope signatures, are associated with both abrupt hydrological change in the tropics (e.g. Heinrich Events) and rapid increases in northern hemisphere temperature (DO events). These events can be linked to modes of variability during the last deglaciation, thus suggesting that drivers of millennial and centennial CO2 variability during both periods are intimately linked to abrupt climate variability.