Historically, classroom content delivery has relied on lecture, but recently there has been a call for educators to use active learning to promote student engagement and a deeper understanding of the material (Bonwell and Eison 1991; Erickson 1984; Cross 1987; Prince 2004; Bodnar and Clark 2014). According to Prince (2004) active learning is any method that promotes engagement with the material through activities and requires students to think about what they are doing. This mixed methods study used Game-Based Learning as an active learning methodology to embed 21st Century Skills and epistemic frames into the domain content of a Bioengineering Senior Design Course. The control section was taught primarily with seventy-five minute lectures and the intervention section used a flipped classroom approach where in-class time focused on games and activities. The intervention was developed using Game-Based Learning (GBL) as the pedagogy within the Cognitive Apprenticeship framework. The framework is based on the traditional model of apprenticeship where students learn how to replicate the thought processes of an industry professional and then apply those techniques to their own project (Collins and Kapur 2014; Pieters and de Bruijn 1992; Mitterer and John 2006; Stalmeijer 2015). The quantitative data indicated that students from both sections of the course learned acceptable levels of domain content. However, qualitative data which included student reflections and semi-structured interviews did indicate that students in the intervention section developed a better understanding of 21st Century Skills. This led us to the conclusion that Game-Based Learning within the Cognitive Apprenticeship model can be used as a valuable classroom tool for delivering curriculum in senior design courses.