We present source estimates of atmospheric carbon monoxide from nonmethane volatile organic compound (NMVOC) oxidation during a period of 8 years (1997–2004) using a Bayesian inversion analysis. The optimized global NMVOC-derived CO source strength indicates a change of a factor of 2 between the 1997–1998 strong El Niño and subsequent La Niña conditions. For comparison, the average 8 year interannual variability (IAV) is 18%. The variation of NMVOC-derived CO is closely correlated with the Oceanic Niño Index (ONI) and surface temperature. A time-lagged correlation analysis between ONI and NMVOC-derived CO inventory indicated El Niño/Southern Oscillation leads the Northern Hemisphere (NH) NMVOC-derived CO production by about 3 months earlier than the Southern Hemisphere's (SH). The SH NMVOC-derived CO was positively correlated with the lagged-ONI (r = 0.57), while the temperature change barely influenced SH NMVOC-derived CO (r = 0.01). In the NH, temperature was more robustly correlated with NMVOC-derived CO (r = 0.58) than the lagged-ONI (r = 0.35). In particular, the extra-tropical temperature showed a strong correlation (r = 0.90) with the NH NMVOC-derived CO and suggested its primary role in controlling the interannual variability of the NH NMVOC-derived CO.