Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (O2peak) with aerobic training. Research Question The goal of this study was to investigate the effect of aerobic training and exercise prescription on O2peak in COPD. Study Design and Methods A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring O2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome. Results A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in O2peak (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in O2peak was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in O2peak was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect O2peak. Cohorts with more severe airflow obstruction exhibited smaller improvements in O2peak (P < .001). Interpretation Overall, people with COPD achieved moderate improvements in O2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population. Clinical Trial Registration PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/