Acidification, deoxygenation, and warming are escalating changes in coastal waters throughout the world ocean, with potentially severe consequences for marine life and ocean-based economies. To examine the influence of these oceanographic changes on a key biological process, we measured the effects of current and expected future conditions in the California Current Large Marine Ecosystem on the fertilization success of the red abalone (Haliotis rufescens). Laboratory experiments were used to assess abalone fertilization success during simultaneous exposure to various levels of seawater pH (gradient from 7.95 to 7.2), dissolved oxygen (DO) (˜60 and 180 μm.kg SW) and temperature (9, 13, and 18 °C). Fertilization success declined continuously with decreasing pH but dropped precipitously below a threshold near pH 7.55 in cool (9 °C—upwelling) to average (13 °C) seawater temperatures. Variation in DO had a negligible effect on fertilization. In contrast, warmer waters (18 °C) often associated with El Niño Southern Oscillation conditions in central California acted antagonistically with decreasing pH, largely reducing the strong negative influence below the pH threshold. Experimental approaches that examine the interactive effects of multiple environmental drivers and also strive to characterize the functional response of organisms along gradients in environmental change are becoming increasingly important in advancing our understanding of the real-world consequences of changing ocean conditions.