Co-existence of toxic metals causes complex toxicity to microorganisms during bioremediation in water and soil. This study investigated the immobilization of Pb2+ and Cd2+ by fungus Aspergillus niger, which has been widely applied to environmental remediation. Five treatments were set, i.e., CK (no toxic metals), Pb2+ only, Cd2+ only, Pb2+/Cd2+ = 1:1(molar ratio), and Pb2+/Cd2+ = 2:1. Cadmium induced strong toxicity to the fungus, and maintained the high toxicity during incubation. However, as Pb/Cd ratio increased from 0 to 2, the removal rates of Cd2+ by A. niger were raised from 30 to 50%. The elevated activities of pyruvate dehydrogenase (PDH) and citrate synthetase (CS) enzymes confirmed that Pb addition could stimulate the growth of A. niger. For instance, citric acid concentrations and CS activities were 463.22 mg/L and 78.37 nmol/min/g, respectively, during 3-day incubation as Pb/Cd = 1. However, these two values were as low as similar to 50 with addition of only Cd. It was hence assumed that appropriate co-existence of Pb2+ enhanced microbial activity by promoting TCA cycle of the fungus. Moreover, the SEM analysis and geochemical modeling demonstrated that Pb2+ cations were more easily adsorbed and mineralized on A. niger with respect to Cd2+. Therefore, instead of intensifying metal toxicity, the addition of appropriate Pb actually weakened Cd toxicity to the fungus. This study sheds a bright future on application of A. niger to the remediation of polluted water with co-existence of Pb and Cd.