This article reports a synthesis and meta-analysis of intervention studies investigating the effects of team-based learning on content knowledge outcomes. Team-based learning is a particular set of instructional components most often used in higher education classrooms. Authors of team-based learning reviews report that team-based learning improves students’ end of course grades, test performance, and classroom engagement. Students report that team-based learning is interesting, allows for deeper understanding of content, and prepares them more effectively for assessment and course performance. A total of 30 studies were located and synthesized. In total, 17 studies met criteria for a meta-analysis, yielding a mean effect size estimate of 0.55, p < 0.001 across all measures. Moderator analysis indicated that group size moderated the magnitude of effect to a statistically significant degree, with smaller group sizes contributing to additional effects. The meta-analysis is followed by a confirmatory synthesis of the remaining 13 studies. Implications for instruction incorporating the use of team-based learning are described.