Regional processes play a key role in the global carbon budget. Major ocean CO2 uptake at mid-latitudes counteracts CO2 release in the tropics, which is modulated by episodes of marine heatwaves. Yet, we lack essential knowledge on persistent marine heatwaves, and their effect on the CO2 sensitive areas. Here we show, using a 1985–2017 joint analysis of reconstructions, ocean reanalysis and in situ and satellite data, that persistent marine heatwaves occur in major CO2 uptake and release areas. Average air-sea CO2 flux density changes from persistent marine heatwaves are strongest in the Pacific Ocean with a 40 ± 9% reduction in CO2 release in the tropics linked to ENSO, and a reduction in CO2 uptake of 29 ± 11% in the North Pacific over the study period. These results provide new insights into the interplay of extreme variability and a critical regulating ocean ecosystem service, and pave the way for future investigations on its evolution under climate change.