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Presently, the Indian Ocean (IO) resides in a climate state that prevents strong year-to-year climate variations. This may change under greenhouse warming, but the mechanisms remain uncertain, thus limiting our ability to predict future changes in climate extremes. Using climate model simulations, we uncover the emergence of a mode of climate variability capable of generating unprecedented sea surface temperature and rainfall fluctuations across the IO. This mode, which is inhibited under present-day conditions, becomes active in climate states with a shallow thermocline and vigorous upwelling, consistent with the predictions of continued greenhouse warming. These predictions are supported by modeling and proxy evidence of an active mode during glacial intervals that favored such a state. Because of its impact on hydrological variability, the emergence of such a mode would become a first-order source of climate-related risks for the densely populated IO rim.