AbstractStratospheric water vapor increases are expected in response to greenhouse gas-forced climate warming, and these changes act as a positive feedback to surface climate. Previous efforts at inferring trends from the 3–4 decade-long observational stratospheric water vapor record have yielded conflicting results. Here we show that a robust multi-decadal variation of water vapor concentrations exists in most parts of the stratosphere based on satellite observations and atmospheric model simulations, which clearly divides the past 40 years into two wet decades (1986–1997; 2010–2020) and one dry decade (1998–2009). This multi-decadal variation, especially pronounced in the lower to middle stratosphere and in the northern hemisphere, is associated with decadal temperature anomalies (±0.2 K) at the cold point tropopause and a hemispheric asymmetry in changes of the Brewer-Dobson circulation modulating methane oxidation. Multi-decadal variability must be taken into account when evaluating stratospheric water vapor trends over recent decades.