The degradation of cyanobacterial blooms often causes hypoxia and elevated concentrations of ammonia, which can aggravate the adverse effects of blooms on aquatic organisms. However, it is not clear how one stressor would work in the presence of other coexistent stressors. We studied the toxic effects of elevated ammonia under hypoxia using a common yet important cladoceran species Daphnia similis isolated from heavily eutrophicated Lake Taihu. A 3 × 2 factorial experimental design was conducted with animals exposed to three un-ionized ammonia levels under two dissolved oxygen levels. Experiments lasted for 14 days and we recorded the life-history traits such as survival, molt, maturation, and fecundity. Results showed that hypoxia significantly decreased survival time and the number of molts of D. similis, whereas ammonia had no effect on them. Elevated ammonia significantly delayed development to maturity in tested animals and decreased their body sizes at maturity. Both ammonia and hypoxia were significantly detrimental to the number of broods, the number of offspring per female, and the number of total offspring per female, and significantly synergistic interactions were detected. Our data clearly demonstrate that elevated ammonia and hypoxia derived from cyanobacterial blooms synergistically affect the cladoceran D. similis.