Past studies have suggested that young people lack knowledge regarding food safety, and that food safety education is appropriate for integration into science education since it often involves science knowledge. Thus, this study combined the methods of inquiry-based and game-based learning to develop a computer detective game, called the Poison Riddle, that makes students actively explore food safety knowledge through playing the role of a science detective to solve a task related to food poisoning at home in a virtual world. To evaluate the learning effectiveness of this game, 109 high school students were selected as the research participants. The research findings indicated that this game could help students improve their microbial food safety knowledge. Most students had positive participation perception and gaming behaviors related to the game. In addition, the analysis indicated that the students who successfully solved the game task gained more positive gaming behaviors, food safety knowledge, and significant sequential behaviors compared to those who were unsuccessful in solving the game task.