Seasonal hypoxia in the bottom waters of the Peter the Great Bay (PGB) of the Japan/East Sea (JES) occurs in summer. Using the empirical relationship between dissolved oxygen (DO) and pH obtained for hypoxic conditions and available historical DO data, acidification rates were estimated. Carefully sampled time-series observations from the northwestern part of the JES, carried out from 1999 to 2014 along the 132°20′ E and 134°00′ E longitudes, were chosen to determine the interannual variability of the sea’s hydrochemical parameters (DO, pH, and TA—the total alkalinity phosphates, nitrate, and silicates). To limit the effects of seasonal and spatial variability, only data obtained in the warm period were used. Additionally, all data from depths shallower than 500 m were discarded because they are affected by high natural variability, mostly due to strong mesoscale dynamic structures. Our results demonstrated that the pH and DO concentrations measured in the Upper Japan Sea Proper Water (750 m), Lower Japan Sea Proper Water (1250, 1750, 2250 m), and Bottom Water (3000 m) have been decreasing in recent years. On the other hand, calculated normalized dissolved inorganic carbon (NDIC), CO2 partial pressure (pCO2), and measured nutrient concentrations have been increasing. Maximum rates of acidification and deoxygenation are occurring at around 750 m. The annual rate of increase of pCO2 in the water exceeds the atmospheric rate more than 2-fold at a depth of 750 m. The observed variability of the hydrochemical properties can be explained by the combination of the slowdown ventilation of the vertical water column and eutrophication. However, the results obtained here are valid for the subpolar region of the JES, not for the whole sea. The synchronization of the deoxygenation of the open part of the JES and PGB has been found.