We evaluated how climate influences interannual variability in the terrestrial Net Ecosystem Exchange (NEE) of CO2 using the Simple Biosphere Model, Version 2 (SiB2) for 1983 to 1993 on a global, 1¿ by 1¿ latitude/longitude grid with a 10-min time step. We quantified climate influences on NEE, explained regional differences, and related NEE variability to the Arctic Oscillation (AO) and the El Ni¿o-Southern Oscillation (ENSO). The simulated NEE reproduces the salient features and magnitude of the measured global CO2 growth rate. The Northern Hemisphere shows a pattern of alternating positive and negative NEE anomalies that cancel such that the tropics dominate the global simulated NEE interannual variability. Climate influences have strong regional differences with precipitation dominating in the tropics and temperature in the extratropics. In tropical regions with drier soils, precipitation control of photosynthesis (i.e., drought stress) dominates; in nearly saturated soils, precipitation control of respiration dominates. Because of cancellation and competing effects, no single climate variable controls global or regional NEE interannual variability. Globally, precipitation accounts for 44% of NEE variability; followed by Leaf Area Index (23%), soil carbon (12%), and temperature (16%). The influence of ENSO on NEE variability is consistent with that expected for shifting precipitation patterns in the tropics. Except in northern Europe, temperature advection by the AO does not significantly influence NEE variability. Neither the AO nor ENSO fully explain the temperature influence on respiration or the simulated NEE anomaly pattern in the Northern Hemisphere.