The purpose of this case study was to investigate how pre-service chemistry teachers' science teaching orientations change during a two-semester intervention designed to enhance their pedagogical content knowledge (PCK) for teaching the nature of science (NOS). Moreover, the way that pre-service chemistry teachers translated their change in orientation into both their instructional planning and their PCK was examined. Thirty pre-service chemistry teachers enrolled in a Research in Science Education course participated in the study. Responses to an open-ended instrument, interviews, observations, and documents such as lesson plans and reflection papers were used as qualitative data sources. Through in-depth analysis of explicit PCK and further deductive analysis, we identified the influence of the intervention on participants' orientation and how participants translated their orientation into their planning and PCK. Analysis of data revealed that most of the pre-service teachers' naïve and transitional views about NOS changed into informed ideas after explicit-reflective NOS instruction. Participants revised their science teaching orientations by including more reform-based orientations at the end of the course (i.e., teaching NOS-related orientations). Their plans included at least one NOS aspect as an objective, which indicates that all of the participants designed their lesson plans with more informed views about at least one NOS aspect. In terms of aligning their reform-based orientations with other PCK components, pre-service chemistry teachers were more able to align their orientation with knowledge of instructional strategy and assessment than with knowledge of the learner. Implications for science teacher education and research are discussed.