In science education, inquiry-based approaches to teaching and learning provide a framework for students to building critical-thinking and problem-solving skills. Teacher professional development has been an ongoing focus for promoting such educational reforms. However, despite a strong consensus regarding best practices for professional development, relatively little systematic research has documented classroom changes consequent to these experiences. This paper reports on the impact of sustained, multiyear professional development in a program that combined neuroscience content and knowledge of the neurobiology of learning with inquiry-based pedagogy on teachers’ inquiry-based practices. Classroom observations demonstrated the value of multiyear professional development in solidifying adoption of inquiry-based practices and cultivating progressive yearly growth in the cognitive environment of impacted classrooms.