Inducible defenses of prey are evolved under diverse and variable predation risks. However, during the co-evolution of prey and multiple predators, the responses of prey to antagonistic predation risks, which may put the prey into a dilemma of responding to predators, remain unclear. Based on antagonistic predation pressure from an invertebrate (Chaoborus larvae) and a vertebrate (Rhodeus ocellatus) predator, we studied the responses of multiple traits and transcriptomes of the freshwater crustacean Ceriodaphnia cornuta under multiple predation risks. Chaoborus predation risk altered the expression of genes encoding cuticle proteins and modulated the biosynthesis of steroid hormones, cutin, suberine, and wax, leading to the development of horns and increase in size at the late developmental stage. Meanwhile, fish predation risk primarily triggered genes encoding ribosomes and those involved in unsaturated fatty acid biosynthesis and cysteine and methionine metabolism, resulting in smaller individual size and earlier reproduction. Inducible responses of both transcriptome and individual traits revealed that predator-dependent unique responses were dominant and the dilemma of antagonistic responses was relatively limited. However, the unique individual traits in response to invertebrate predation could be significantly impaired by vertebrate predation risk, even though the unique responses to different predators were extremely weakly correlated and could be elicited simultaneously. These results indicate that diverse predator-dependent unique responses are favored by Ceriodaphnia during its co-evolution with multiple predators. Nonetheless, Ceriodaphnia is not a generalist that can fully adopt all predator-dependent unique responses simultaneously under multiple predation risks.