The seasonal upwelling along the west coast of India (WCI) brings nutrient-rich, oxygen-poor subsurface waters to the continental shelf, favoring very low oxygen concentrations in the surface waters during late boreal summer and fall. This yearly-recurring coastal hypoxia is more severe during some years, leading to coastal anoxia that has strong impacts on the living resources. In the present study, we analyze a 1/4° resolution coupled physical–biogeochemical regional oceanic simulation over the 1960–2012 period to investigate the physical processes influencing the oxycline interannual variability off the WCI, that being a proxy for the variability on the shelf in our model. Our analysis indicates a tight relationship between the oxycline and thermocline variations in this region on both seasonal and interannual timescales, thereby revealing a strong physical control of the oxycline variability. As in observations, our model exhibits a shallow oxycline and thermocline during fall that combines with interannual variations to create a window of opportunity for coastal anoxic events. We further demonstrate that the boreal fall oxycline fluctuations off the WCI are strongly related to the Indian Ocean Dipole (IOD), with an asymmetric influence of its positive and negative phases. Positive IODs are associated with easterly wind anomalies near the southern tip of India. These winds force downwelling coastal Kelvin waves that propagate along the WCI and deepen the thermocline and oxycline there, thus preventing the occurrence of coastal anoxia. On the other hand, negative IODs are associated with WCI thermocline and oxycline anomalies of opposite sign but of smaller amplitude, so that the negative or neutral IOD phases are necessary but not the sufficient condition for coastal anoxia. As the IODs generally start developing in summer, these findings suggest some predictability to the occurrence of coastal anoxia off the WCI a couple of months ahead.