To investigate biomarkers representing the physiological and biochemical responses of the brackish-water clam Corbicula japonica, we conducted a full factorial-design experiment to test different water-temperature levels (20 °C and 25 °C), salinity levels (5 and 20 psu), and food-availability levels (0.5 and 2.0 mg suspended solids (SS)·ind⁻¹·d⁻¹). Increase in water temperature significantly decreased superoxide dismutase (SOD) and catalase (CAT) activities and oxyradical-absorbance capacity (ORAC), leading to lipid peroxidation (i.e., oxidative damage). Salinity activated or inhibited these biochemical markers. Food availability supported a detoxification mechanism against oxidative stress. Principal-components and cluster analyses revealed that a total of eight experimental conditions fell into three groups related to water temperature and/or salinity. The shift from Group I (20 °C water temperature) to Group II (25 °C water temperature and 5-psu salinity) demonstrated that the condition index, SOD, CAT, and ORAC had significantly decreased. With the further shift to Group III (25 °C water temperature and 20-psu salinity), we found a prominent increase in ORAC, which led to oxidative damage but no mortality. We conclude that future habitat changes driven by global warming should be closely watched, particularly given that local anthropogenic disturbances further add to natural ones.