Dissolved oxygen (DO) is a key biogeochemical control in coastal systems, and its concentration and drivers vary markedly through time and space. This makes it difficult to accurately represent coastal DO and associated biogeochemical processes in models, limiting our ability to predict how these systems will respond to global change. We obtained high‐frequency (5‐min) in situ measurements of DO collected at three locations across the interface of a tidal creek and coastal marsh in the Pacific Northwest, USA. Random Forest machine learning models quantified the importance of three categories of environmental drivers (Aquatic, Climatic, and Terrestrial) of DO variability across the creek–marsh interface. We selected two 4‐month datasets representing Summer and Winter seasonal periods to test two hypotheses on the dominant drivers of DO at the coastal interface. We found that the Terrestrial driver—characterized by long periods of anaerobic conditions and episodic pulses in DO after floods—was most important during the Winter, whereas the Aquatic driver—characterized by variability over tidal, diel, and lunar cycles—was most important during the Summer. We explored how future climate change scenarios could alter the drivers of DO variability using a cumulative sums driver–response framework. Our results suggest that under climate change, Aquatic and Climatic drivers may increase in importance during the Summer, potentially linked to changing metabolic regimes and sea level, with Terrestrial driver importance potentially increasing during the Winter. Our approach highlights useful methods for understanding the spatiotemporal complexity of oxygen across coastal interfaces and quantifying the relative importance of distinct environmental drivers.