Process oriented guided inquiry learning (POGIL) is a specific type of active learning centered on a learning cycle where students first explore a concept through scientific models, followed by a concept invention, and finally a concept application phase. In spite of POGIL’s research-based design and the many studies showing it increases learning outcomes, there is still a critical gap in the knowledge behind the effect of POGIL in attitudinal factors and the mechanisms behind it. The current study seeks to build an understanding of the mechanistic ways in which POGIL works and its effect on students’ attitudes and learning. The sample consisted of students who enrolled in General Chemistry I in the Fall semester across 7 sections (classrooms) at an R1 (large research) university in the eastern part of the US. Four sections used POGIL instruction (N = 809) while the other three used Traditional teaching methods (N = 543). Statistical models using multilevel statistics show students in the POGIL condition had higher chemistry identity, competency beliefs, and chemistry grades. Furthermore, performance in General Chemistry I appeared to be a core mediator of all the observed differences in General Chemistry II where students in the POGIL condition still performed better and had higher chemistry-related attitudes.