This study aimed to explore the relationship between science teachers' pedagogical content knowledge (PCK) of argumentation, epistemological beliefs, and classroom practices. Participants were three urban science teachers who were selected among 12 teachers from a professional development (PD) program focusing on Argument-Driven Inquiry (ADI) instructional model. These three teachers completed PCK of argumentation assessments; they were observed while implementing the argumentation investigations and reflected on and interviewed about their teaching experiences after each enactment and at the end of the study. The findings illustrate that these teachers experience positive shifts in their PCK of argumentation; a teacher with evaluativist epistemological beliefs has high-quality PCK of argumentation, which is reflected in her teaching practices aligning with the expectations of the ADI model. However, if teachers' epistemology included multiplist elements, they modify the ADI investigations even though they have improved their PCK of argumentation. This finding addresses how teachers' epistemological beliefs are connected to their teaching actions. The results show that different aspects of epistemological beliefs and PCK of argumentation are linked to teachers' use of argumentation investigations. The paper discusses the implications for science education and future research.