The hydroxyl radical (OH) is the primary oxidant in the troposphere, and the impact of its fluctuations on the methane budget has been disputed in recent years, however measurements of OH are insufficient to characterize global interannual fluctuations relevant for methane. Here, we use a 6,000-y control simulation of preindustrial conditions with a chemistry-climate model to quantify the natural variability in OH and internal feedbacks governing that variability. We find that, even in the absence of external forcing, maximum OH changes are 3.8 ± 0.8% over a decade, which is large in the context of the recent methane growth from 2007-2017. We show that the OH variability is not a white-noise process. A wavelet analysis indicates that OH variability exhibits significant feedbacks with the same periodicity as the El Niño-Southern Oscillation (ENSO). We find intrinsically generated modulation of the OH variability, suggesting that OH may show periods of rapid or no change in future decades that are solely due to the internal climate dynamics (as opposed to external forcings). An empirical orthogonal function analysis further indicates that ENSO is the dominant mode of OH variability, with the modulation of OH occurring primarily through lightning [Formula: see text] La Niña is associated with an increase in convection in the Tropical Pacific, which increases the simulated occurrence of lightning and allows for more OH production. Understanding this link between OH and ENSO may improve the predictability of the oxidative capacity of the troposphere and assist in elucidating the causes of current and historical trends in methane.