Practical work in secondary science education is often organized through closed “cookbook” protocols that constrain students’ autonomy and limit the development of scientific thinking. This study examines the impact of two instructional approaches to a DNA extraction activity in Biology and Geology: A cookbook-style laboratory practice and an inquiry-based science education (IBSE) activity. A mixed-methods design was implemented, combining a pre–post-test component within each group with a comparison between two non-randomized cohorts of students in the 4th year of compulsory secondary education in Spain (n = 45). Academic performance was assessed through a multiple-choice test, self-perceived critical thinking and satisfaction were measured using validated questionnaires, and meaningful learning was explored through qualitative analysis of delayed open-ended responses. Both approaches led to improvements in immediate academic performance. However, only students in the inquiry-based condition showed evidence of deeper conceptual understanding, explicit references to the scientific method and a sustained perception of meaningful learning. These findings highlight the potential of IBSE-oriented laboratory work to foster not only scientific literacy and deep learning, but also transferable competences relevant for science-related vocational pathways.