Objective: This study aimed to examine (1) the independent effects of hypoxia on cognitive function and (2) the effects of exercise on cognition while under hypoxia. Methods: Design: Systematic review with meta-analysis. Data sources: PubMed, Scopus, Web of Science, PsychInfo, and SPORTDiscus were searched. Eligibility criteria for selecting studies: randomized controlled trials and nonrandomized controlled studies that investigated the effects of chronic or acute exercise on cognition under hypoxia were considered (Aim 2), as were studies investigating the effects of hypoxia on cognition (Aim 1). Results: In total, 18 studies met our inclusionary criteria for the systematic review, and 12 studies were meta-analyzed. Exposure to hypoxia impaired attentional ability (standardized mean difference (SMD = –0.4), executive function (SMD = –0.18), and memory function (SMD = –0.26) but not information processing (SMD = 0.27). Aggregated results indicated that performing exercise under a hypoxia setting had a significant effect on cognitive improvement (SMD = 0.3, 95%CI: 0.14 – 0.45, I = 54%, p < 0.001). Various characteristics (e.g., age, cognitive task type, exercise type, exercise intensity, training type, and hypoxia level) moderated the effects of hypoxia and exercise on cognitive function. Conclusions: Exercise during exposure to hypoxia improves cognitive function. This association appears to be moderated by individual and exercise/hypoxia-related characteristics.