Abstract The hydroxyl radical (OH) is a key oxidant for methane. Previous studies suggest that OH exhibits interannual variability linked to the El Nino–Southern Oscillation (ENSO), but the sign, magnitude, and underlying mechanisms of this response remain uncertain. We diagnose changes in OH using the CAM‐chem chemistry–climate model with prescribed sea surface temperature composites corresponding to ENSO phases. We find a weak but statistically significant 2.3% decrease in tropical tropospheric air‐mass‐weighted OH during El Nino, and no significant change during La Nina. During El Nino, this net decline in OH is driven by enhanced biogenic and biomass burning emissions, while the direct meteorological contribution is negligible. Lightning‐produced NO emissions and their associated effects on OH are indistinguishable from atmospheric variability during both ENSO phases. Our results indicate that biogenic emissions play a significant but previously underappreciated role in regulating interannual variability in OH and the global methane budget.