Lightning increases the atmosphere’s ability to cleanse itself by producing nitric oxide (NO), leading to atmospheric chemistry that forms ozone (O3) and the atmosphere’s primary oxidant, the hydroxyl radical (OH). Our analysis of a 2012 airborne study of deep convection and chemistry demonstrates that lightning also directly generates the oxidants OH and the hydroperoxyl radical (HO2). Extreme amounts of OH and HO2 were discovered and linked to visible flashes occurring in front of the aircraft and to subvisible discharges in electrified anvil regions. This enhanced OH and HO2 is orders of magnitude greater than any previous atmospheric observation. Lightning-generated OH in all storms happening at the same time globally can be responsible for a highly uncertain, but substantial, 2 to 16% of global atmospheric OH oxidation.