Ocean acidification evolves on the background of a natural ocean pH gradient that is the result of the interplay between ocean mixing, biological production and remineralization, calcium carbonate cycling, and temperature and pressure changes across the water column. While previous studies have analyzed these processes and their impacts on ocean carbonate chemistry, none have attempted to quantify their impacts on interior ocean pH globally. Here we evaluate how anthropogenic changes and natural processes collectively act on ocean pH, and how these processes set the vulnerability of regions to future changes in ocean acidification. We use the mapped data product from the Global Ocean Data Analysis Project version 2, a novel method to estimate preformed total alkalinity based on a combination of a total matrix intercomparison and locally interpolated regressions, and a comprehensive uncertainty analysis. We find that the largest contribution to the interior ocean pH gradient comes from organic matter remineralization, with CaCO₃ cycling being the second most important process. The estimates of the impact of anthropogenic CO₂ changes on pH reaffirm the large and well-understood anthropogenic impact on pH in the surface ocean, and put it in the context of the natural pH gradient in the interior ocean. We also show that in the depth layer 500–1,500 m natural processes enhance ocean acidification by on average 28 ± 15%, but with large regional gradients.