Challenges in training faculty in inquiry-based, learner-centered instruction include empirically evaluating the efficacy of training in teaching and sustaining long-term support for change. We developed the Faculty Institutes for Reforming Science Teaching (FIRST IV) model to provide new approaches to professional development in biology instruction for postdoctoral scholars. The goal was to develop early-career faculty who value and implement evidence-based pedagogies that facilitate learning. We report the activities and outcomes of FIRST IV, using comprehensive evidence derived from expert reviews of participants’ teaching, self-reported data from participants and students, and comparisons with non-project faculty. Participants completed a workshop twice in two years, followed by teaching an entire or partial course at their institution and sustained mentoring by STEM education experts. Postdocs showed belief in learner-centered teaching, and 74% taught using primarily learner-centered practices. We followed a subset of participants into their first faculty positions and quantified how their instructional design and student assessments differed from a colleague at the same institution. External review of teaching indicated that FIRST IV faculty practiced significantly more learner-centered instruction and used more collaborative learning than their colleagues. We conclude that the FIRST IV model offers significant and unique contributions to current challenges in professional development in STEM education