A flipped classroom is one where students are first introduced to content outside of the classroom. This frees up class time for more active learning strategies and has been shown to enhance student learning in high school and college classrooms. However, many studies in General Chemistry, a college gateway science course, were conducted in small classes and in selective institutions. In this article, we describe our approach to flipping the General Chemistry sequence at two different colleges within the City University of New York, a large, urban public university system. Our results indicate that the flipped model leads to increased student performance (compared with a traditional lecture model) in both institutions. The results are robust across class size (from 20 to 1,000) and for different instructors and different student demographics, with an increased benefit observed for students who are potentially less well-prepared on entering college.