The aim of the present study was to examine the effects of a gamification-based program on cardiorespiratory fitness (CRF) levels of college students. We divided 112 college students into an intervention group (IG) and a control group (CG). IG college students followed a 15-week gamification-based program, whereas CG followed traditional lectures. CRF was assessed using the 20-meter shuttle-run test. CRF significantly improved after the program in the IG compared to CG (d ≤ 0.94, < 0.001). Only participants of IG had significant CRF improvements (d ≤ 0.87, < 0.001) between pre- and post-assessments. In the IG, from the students who attended 100% of lectures, 87.8% met physical activity recommendations for 100% of weeks, whereas from those who attended <100%, only 26.7% met them them for 100% of weeks ( < 0.001). Participants who met recommendations 100% of weeks had a significant CRF improvement ( < 0.001). Motivating college students throughout innovative teaching methods (e.g., gamification) can lead to health improvements.