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The flipped classroom instructional strategy is thought to be a good way to structure learning experiences to improve student learning outcomes. Many studies have been conducted to examine the effects of flipped classroom on student learning outcomes compared to the traditional classroom, but the results were inconclusive. The purpose of this study was to examine the overall effect of the flipped classroom instructional strategy on student learning outcomes in relation to a set of moderating variables including student levels, publication types, study durations, and subject area. This meta-analysis examined studies that compared classrooms that used the flipped classroom instructional strategy and classrooms that did not. Seventeen databases were searched to identify literature meeting our inclusion criteria and resulted in 55 publications with 115 effect size comparisons on cognitive student learning outcomes published between 2000 and 2016. Overall, we found a statistically significant effect size (g = 0.193; p < .001; with a 95% confidence interval of 0.113–0.274) in favor of the flipped classroom instructional strategy. The effect size data were normally distributed and exhibited statistically significant heterogeneity. The effect sizes were significantly moderated by subject area such as mathematics, science, social sciences, engineering, arts and humanities, health, and business. No evidence of publication bias was detected in these data. A full discussion of the findings and implications for educational practice and research were provided.