Estuarine acidification caused by outflows from acid sulfate soils (ASS), impacts many estuaries in eastern Australia. Affected waters are characterized by low pH and elevated concentrations of metals, particularly iron, aluminum, and manganese. The effects of low pH and elevated metals, associated with ASS-affected water, on adult Sydney rock oysters Saccostrea glomerata have not been previously studied in detail. Most production of Sydney rock oysters occurs in estuaries along the Australian east coast and has significantly decreased over the last 30 y. To investigate poor oyster production in particular areas of the Manning River, New South Wales, Australia, associations between ASS drainage water, estuarine acidification, and Sydney rock oyster survival and growth were studied. This involved a seven-month field study where water quality and oyster survival and growth was measured at seven sites differentially impacted by ASS-affected waters. Estuarine acidification on the Manning River followed periods of heavy rainfall and caused widely fluctuating pH levels, combined with low electrical conductivities and high concentrations of iron and aluminum at experimental sites selected to expose Sydney rock oysters to ASS-affected waters. Hydrologic characteristics and location of experimental sites controlled the extent of impact caused by ASS-affected waters. Sites exposed to ASS-affected waters had a significantly higher (P < 0.001) level of oyster mortality. Mortalities in small oysters were significantly higher (P < 0.05) than mortalities in large oysters. This was attributed to acid-induced shell degradation, which eventually caused perforation of the thinner shells of small oysters. Mortalities of small oysters increased after 42 days of exposure. ASS-affected waters also significantly reduced large and small oyster growth (P < 0.001). Growth of oysters improved and mortalities stabilized at sites impacted by ASS-affected waters in dryer periods because of the improvement in water quality.