Although we have numerous publications about the effect of fractional CO laser therapy for burn scars, quantitative data about its efficacy and safety are sparse. The purpose of this meta-analysis was to assess the efficacy and safety of fractional CO laser therapy for the treatment of burn scars. Pertinent studies were identified by a search of PubMed, Embase and Web of Science up to 20 September 2020. Weighted mean difference (WMD) was conducted to combine the results, and a random-effect model was used to pool the results. Publication bias was estimated using Begg and Egger's regression asymmetry test. Twenty articles were included. Our pooled results suggested that fractional CO laser therapy significantly improved the Vancouver Scar Scale (VSS) score (WMD = -3.24, 95%CI: -4.30, -2.18; P < 0.001). Moreover, the Patient and Observer Scar Assessment Scale (POSAS)-patient (WMD = -14.05, 95%CI: -22.44, -5.65; P = 0.001) and Observer (WMD = -6.31, 95%CI: -8.48, -4.15; P < 0.001) also showed significant improvements with the treatment of fractional CO laser therapy. Fractional CO laser significantly reduced scar thickness measured with ultrasonography (WMD = -0.54, 95%CI: -0.97, -0.10; P < 0.001). For other outcomes, including pigmentation, vascularity, pliability, and height of scar, vascularity and relief, laser therapy was associated with significant improvements. However, only the cutometer measure R2 (scar elasticity) (WMD = -0.06, 95%CI: -0.10, -0.01; P = 0.023) was significantly improved with the laser therapy, but cutometer measures R0 (scar firmness) (WMD = 0.03, 95%CI: -0.04, 0.09; P = 0.482) was not. Side effects and complications induced by fractional CO laser were mild and tolerable. Fractional CO laser therapy significantly improved both the signs and symptoms of burn scars. Considering potential limitations, more large-scale, well-designed RCTs are needed to verify our findings.