Introduction: Transformative Environmental Education and the One Health approach are key perspectives in initial teacher education for responding to the current ecosocial crisis. Objective: This study aims to evaluate the impact of a Teaching–Learning Sequence that employs a serious game (Escape Box) as the central didactic tool to address marine plastic pollution. Methodology: A quasi-experimental design was implemented in the Environmental Education course, using pre- and post-questionnaires administered to 27 fourth-year students, aged between 22 and 23, enrolled in the Primary Education degree at the University of Cádiz (Spain). The Teaching–Learning Sequence was designed following a learning cycle grounded in socioconstructivist principles, integrating Ocean Literacy and the One Health approach. Results: Data analysis shows a significant improvement in the understanding of the socio-environmental issue, although it also reveals the persistence of certain learning obstacles. Conclusions: It is concluded that the use of Escape Boxes, integrated into a socioconstructivist learning cycle and grounded in the Transformative Environmental Education model, has a relevant impact on teacher education. This study not only identifies key conceptual weaknesses related to marine plastic pollution, but also enables future teachers to experience transferable didactic proposals for classroom implementation to address the current ecosocial crisis, adaptable to other socio-environmental issues.