The purpose of this study was to determine the effect of adding game design elements (goal setting, feedback, and external rewards) to an evidence-based physical activity intervention to increase in-class physical activity participation (intensity of activity breaks performed). Nine third- through sixth-grade classrooms (n = 292 students) in one elementary-middle school in Detroit, Michigan (49% female, 95% nonwhite; 80% qualified for free/reduced lunch) participated in this 20-week intervention where teachers implemented 5 × 4 min moderate-to-vigorous activity breaks per day. Gamification of activity breaks occurred during weeks 13–20 of the intervention and included the use of game design elements and classroom goals for activity break intensity. Moderate-to-vigorous physical activity (MVPA) during activity breaks was measured via direct observation. There was a significant effect of intervention with a 27% increase in student MVPA participation during the gamified intervention weeks compared with the standard intervention weeks (p = 0.03). Gamification of activity breaks resulted in 55% (compared with 25% during the standard intervention) of students accumulating approximately 20 min of health-enhancing physical activity per day in their classroom. These findings provide preliminary evidence that gamifying activity breaks may be an important strategy for increasing student participation in classroom activity breaks.