In this study, components, concentrations, distribution characteristics, sources of low-molecular-weight organic acids (LMWOAs) and relationships among the annual hypoxia, LMWOAs and seawater acidification were investigated in the Changjiang Estuary and its adjacent sea area in July 2015. Lactic, acetic and formic acids were detected in the seawater samples in the study area, and their total concentrations (ΣLMWOAs) varied from 0 to 262.6 μmol·L−1, with an average value of 39.2 μmol·L−1. In the surface seawater, high concentration areas of ΣLMWOAs occurred in the sea area near the Changjiang Estuary and the Hangzhou Bay, and north of study area. In the sampling stations along transect A6, high concentration areas of ΣLMWOAs appeared in the bottom seawater of nearshore stations and middle seawater of offshore stations. The terrigenous inputs, especially the Changjiang runoff, were the dominant sources for LMWOAs in the sampling period. The consistency of hypoxia areas, high concentration areas of ΣLMWOAs and low pH value areas in winter and summer suggested that annual hypoxia could cause the long-term seawater acidification by producing LMWOAs in the Changjiang Estuary and its adjacent sea area.