Active learning can engage high school students to learn science, yet there is limited understanding if active learning can help students learn challenging science concepts such as genetics and biotechnology. This quasi-experimental study explored the effects of active learning compared to passive learning regarding high school students' knowledge, motivation and perceptions of learning experiences using The Apple Genomics Project, a National Science Foundation-funded web-based curriculum. Students enrolled in both active learning classrooms and passive learning classrooms utilizing The Apple Genomics Project demonstrated an increase in knowledge of biotechnology and genetics, but did not show change of interest in learning science upon completion of the unit. However, student participants in active learning classrooms had more positive perceptions of learning experiences compared to those students enrolled in the passive learning classrooms. Regardless of the approach used, teachers shared similar perceptions regarding The Apple Genomics Project curriculum, specifically, the biotechnology and genomics unit, including the lesson content, lesson activities, use of technology, and overall impressions of the unit.