Ocean acidification (OA), the global decrease in surface water pH from absorption of anthropogenic CO2, may put many marine taxa at risk. However, populations that experience extreme localized conditions, and are adapted to these conditions predicted in the global ocean in 2100, may be more tolerant to future OA. By identifying locally adapted populations, researchers can examine the mechanisms used to cope with decreasing pH. One oceanographic process that influences pH, is wind driven upwelling. Here we compare two Californian populations of the coral Balanophyllia elegans from distinct upwelling regimes, and test their physiological and transcriptomic responses to experimental seawater acidification. We measured respiration rates, protein and lipid content, and gene expression in corals from both populations exposed to pH levels of 7.8 and 7.4 for 29 days. Corals from the population that experiences lower pH due to high upwelling, maintained the same respiration rate throughout the exposure. In contrast, corals from the low upwelling site had reduced respiration rates, protein content, and lipid-class content at low pH exposure, suggesting they have depleted their energy reserves. Using RNA-Seq, we found that corals from the high upwelling site upregulated genes involved in calcium ion binding and ion transport, most likely related to pH homeostasis and calcification. In contrast, corals from the low upwelling site downregulated stress response genes at low pH exposure. Divergent population responses to low pH observed in B. elegans highlight the importance of multi-population studies for predicting a species’ response to future OA.