Observational studies report a rapid decline of ocean CO2 uptake in the temperate North Atlantic during the last decade. We analyze these findings using ocean physical-biological numerical simulations forced with interannually varying atmospheric conditions for the period 1979–2004. In the simulations, surface ocean water mass properties and CO2 system variables exhibit substantial multiannual variability on sub-basin scales in response to wind-driven reorganization in ocean circulation and surface warming/cooling. The simulated temporal evolution of the ocean CO2 system is broadly consistent with reported observational trends and is influenced substantially by the phase of the North Atlantic Oscillation (NAO). Many of the observational estimates cover a period after 1995 of mostly negative or weakly positive NAO conditions, which are characterized in the simulations by reduced North Atlantic Current transport of subtropical waters into the eastern basin and by a decline in CO2 uptake. We suggest therefore that air-sea CO2 uptake may rebound in the eastern temperate North Atlantic during future periods of more positive NAO, similar to the patterns found in our model for the sustained positive NAO period in the early 1990s. Thus, our analysis indicates that the recent rapid shifts in CO2 flux reflect decadal perturbations superimposed on more gradual secular trends. The simulations highlight the need for long-term ocean carbon observations and modeling to fully resolve multiannual variability, which can obscure detection of the long-term changes associated with anthropogenic CO2 uptake and climate change.