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Abstract The interannual variability of tropical carbon monoxide from the Microwave Limb Sounder over 2004–2018 period is dominated by the quasi‐biennial oscillation (QBO). We simulate the carbon monoxide variability over this period using the 2‐D Caltech/JPL chemistry‐transport model. The chemistry‐transport model includes the photochemical sources and sinks and transport driven by a stream function and eddy diffusivity derived from the assimilated winds of National Centers for Environmental Prediction Reanalysis 2. The results show good agreement between model and Microwave Limb Sounder observations. We also investigate the anomalous period 2015–2016, when the QBO winds deviated significantly from their climatological values. The model simulations could capture the QBO features in agreement with observations for the anomalous period.