Objective To systemically review the clinical application of esketamine for postoperative analgesia in cesarean section. Methods Databases including CNKI, VIP, WanFang Data, PubMed, EMbase, Web of Science, and The Cochrane Library were searched for randomized controlled trials (RCTs) on esketamine in cesarean section from inception to January 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 16 RCTs involving 1 715 cesarean section patients were included. The results of meta-analysis showed that esketamine decreased the patients’ visual analog scale scores after surgery (MD=−0.67, 95%CI −0.86 to −0.49, P<0.000 01) and reduced the need for analgesics for 48 hours after surgery (MD=−2.38, 95%CI −3.15 to −1.62, P<0.000 01) compared with the control drugs (such as opioids, ropivacaine, and normal saline), without increasing adverse reactions such as nausea and vomiting (RR=0.84, 95%CI 0.62 to 1.12, P=0.23), hallucinations (RR=3.00, 95%CI 0.37 to 24.43, P=0.30), drowsiness (RR=1.49, 95%CI 0.16 to 13.99, P=0.73), itching (RR=1.05, 95%CI 0.79 to 1.41, P=0.72), hypotension (RR=0.31, 95%CI 0.04 to 2.40, P=0.26), bradycardia (RR=0.40, 95%CI 0.01 to 11.24, P=0.59), and dizziness (RR=2.24, 95%CI 0.63 to 7.94, P=0.21). Compared with the control drugs, esketamine extended the operation time (MD=2.23, 95%CI 1.73 to 2.74, P<0.000 01), accelerated heart rate (MD=1.31, 95%CI 0.25 to 2.37, P=0.02), and increased the mean arterial pressure (MD=3.88, 95%CI 0.19 to 7.56, P=0.04) during surgery. Additionally, esketamine improved the Apgar score of neonates (MD=0.45, 95%CI 0.26 to 0.63, P<0.000 01) and the Edinburgh postnatal depression scale score of mothers (MD=−1.12, 95%CI −1.87 to −0.55, P=0.000 3), having no effects on the cord blood pH of neonates (MD=0.03, 95%CI −0.01 to 0.07, P=0.14). Conclusion Esketamine has certain advantages when used for postoperative analgesia in cesarean section. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to further verify the above conclusion.