Nitrous oxide (N₂O) is a long-lived potent greenhouse gas and a dominant ozone-depleting substance in the stratosphere. The net marine efflux has been uncertain across decades of global syntheses, with estimates varying widely. The temporal variability and magnitude of emissions from low-oxygen hotspots, such as the Eastern Tropical South Pacific (ETSP), remain poorly constrained due to sparse historical sampling and a lack of independent observational constraints. By assimilating new continuous atmospheric N₂O observations in the Galapagos with Bayesian inverse modeling, we produce the first monthly, spatially resolved, observation-based efflux estimates for the ETSP. We provide an independent benchmark that narrows the widely divergent global efflux products and identifies those that best reproduce the observed atmospheric signal. The resulting estimates resolve the N₂O efflux dynamics during and after the strong 2023–2024 El Niño at spatial and temporal resolutions that sporadic shipboard measurements cannot capture. Peak El Niño conditions appear to suppress ETSP emissions relative to the historical average, while an enhancement in inferred N₂O surface concentrations emerges as the event subsides, driven by upwelling of subsurface waters enriched in N₂O. Although these opposing responses largely balance each other over the full event, the observation-based estimates highlight the value of combining high-frequency atmospheric observations with inverse modeling to refine estimates of marine N₂O effluxes in the future.