Despite multiple studies in the past, seeking to assess the determinants of students' achievement in mathematics, less attention has been paid to the simultaneous role of classroom management (CM), mastery-oriented instructions, and teacher pedagogical content knowledge (PCK). This study, therefore, looked at the mediation effects of mastery-oriented instructions and CM in the relationship between teacher PCK and students' mathematics achievement. The study was a survey and quantitative. A simple random sampling approach was used to select 401 senior high school students from five schools in the Kumasi Metropolis. A structural equation model was used in analyzing the effect of the relationship between the variables. It was concluded that teacher PCK had a significant relationship with students' mathematics achievement. It also had a significant effect on masteryoriented instructions and CM. It was revealed that both teacher PCK and CM did not mediate the relationship between teachers' PCK and students' mathematics achievement.