Background: Game-based learning (GBL) grounded in constructivist and experiential learning theories has emerged as a promising strategy to improve engagement, motivation, and knowledge retention in higher education, particularly within STEM disciplines. Methods: This mixed-methods study evaluated the impact of GBL on student engagement, self-efficacy, and knowledge retention in undergraduate biology and architecture courses—two fields where GBL remains underexplored. Results: Thirty-three students (age 19.6 ± 1.6 years) participated, with near-equal representation from biology (51.4%) and architecture (48.6%) majors. Following GBL implementation, students reported significantly higher levels of engagement, participation, and perceived retention (p < 0.0001; effect size V ≥ 0.43). Biology students demonstrated greater gains in engagement and retention, while architecture students showed stronger improvements in participation and self-confidence. Qualitative feedback highlighted GBL’s interactivity and enjoyability, though some students noted distractions and accountability as challenges. Conclusions: Despite limitations such as small sample size and reliance on self-reported outcomes, the findings suggest that GBL is an effective, student-centered instructional tool with distinct benefits across disciplines. Broader, longitudinal studies using objective assessments are recommended to further validate its impact and inform scalable applications in STEM education.

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