Student-centered strategies are being incorporated into undergraduate classrooms in response to a call for reform. We tested whether teaching in an extensively student-centered manner (many active-learning pedagogies, consistent formative assessment, cooperative groups; the Extensive section) was more effective than teaching in a moderately student-centered manner (fewer active-learning pedagogies, less formative assessment, without groups; the Moderate section) in a large-enrollment course. One instructor taught both sections of Biology 101 during the same quarter, covering the same material. Students in the Extensive section had significantly higher mean scores on course exams. They also scored significantly higher on a content postassessment when accounting for preassessment score and student demographics. Item response theory analysis supported these results. Students in the Extensive section had greater changes in postinstruction abilities compared with students in the Moderate section. Finally, students in the Extensive section exhibited a statistically greater expert shift in their views about biology and learning biology. We suggest our results are explained by the greater number of active-learning pedagogies experienced by students in cooperative groups, the consistent use of formative assessment, and the frequent use of explicit metacognition in the Extensive section.