High‐accuracy spectrophotometric pH measurements were taken during a summer cruise to study the pH dynamics and its controlling mechanisms in the northern Gulf of Mexico in hypoxia season. Using the recently available dissociation constants of the purified m‐cresol purple (Douglas & Byrne, 2017, https://doi.org/10.1016/j.marchem.2017.10.001; Müller & Rehder, 2018, https://doi.org/10.3389/fmars.2018.00177), spectrophotometrically measured pH showed excellent agreement with pH calculated from dissolved inorganic carbon (DIC) and total alkalinity over a wide salinity range of 0 to 36.9 (0.005 ± 0.016, n = 550). The coupled changes in DIC, oxygen, and nutrients suggest that biological production of organic matter in surface water and the subsequent aerobic respiration in subsurface was the dominant factor regulating pH variability in the nGOM in summer. The highest pH values were observed, together with the maximal biological uptake of DIC and nutrients, at intermediate salinities in the Mississippi and Atchafalaya plumes where light and nutrient conditions were favorable for phytoplankton growth. The lowest pH values (down to 7.59) were observed along with the highest concentrations of DIC and apparent oxygen utilization in hypoxic bottom waters. The nonconservative pH changes in both surface and bottom waters correlated well with the biologically induced changes in DIC, that is, per 100‐μmol/kg biological removal/addition of DIC resulted in 0.21 unit increase/decrease in pH. Coastal bottom water with lower pH buffering capacity is more susceptible to acidification from anthropogenic CO2 invasion but reduction in eutrophication may offset some of the increased susceptibility to acidification.