Many biology students struggle to learn about the process of meiosis and have particular difficulty understanding the molecular basis of crossing over and the importance of homologous pairing for proper segregation. To help students overcome these challenges, we designed an activity that uses a newly developed Chromosome Connections Kit® from 3-D Molecular Designs to allow learners to explore meiosis at the molecular level. We took a backwards design approach in constructing an effective classroom activity. We developed evidence-based learning objectives and designed a crossing over activity that targets students' misconceptions and key concepts about meiosis. Assessment questions were designed based on the learning objectives and common student misconceptions. The activity consists of three parts: an interactive introductory video, a model-based activity, and reflection questions. The activity was first beta-tested with a small number of students and revised based on feedback. The revised activity was deployed in a mid-level Cell and Molecular Biology course. Analysis of pre-/post-assessment data from students who completed the activity (n = 83) showed strong learning gains on concepts related to ploidy, homology, segregation, and the mechanism and purpose of crossing over. Additionally, students who participated in the activity outperformed nonparticipants on a Genetics assessment about meiosis the following semester.