Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small cell lung cancer. This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of non-small cell lung cancer (NSCLC) were 47.0% (95% CI: 34.2% - 60.2%) and 80.9% (95% CI: 69.4% - 88.7%), respectively. The combined ORR and DCR for CTLA4 antibody combined with chemotherapy for the treatment of small-cell lung cancer (SCLC) were 65.4% (61.1%-69.5%) and 87.6% (84.5%-90.2%), respectively. The combined six-month progression-free survival rates (PFSRs6m ) for NSCLC and SCLC were 50.2% (95% CI: 21.9% - 78.4%) and 30.7% (21.2%-40.3%), respectively, and the OSRs1y were 56.4% (39.1%-73.7%) and 36.9% (33.3%-40.5%), respectively. In addition, the combined ORR and DCR for the checkpoint inhibitors plus CTLA4 antibody treatment group in NSCLC were 29.6% (95% CI: 11.4%-57.8%) and 48.7% (16.8%-81.7%), respectively. In subgroup analyses, a significant improvement in PFS was observed in NSCLC and SCLC, with a combined hazard ratio and 95% confidence interval of 0.841 (0.737-0.961) and 0.856 (0.756-0.968), respectively. In summary, synergistic activity and an acceptable safety profile were observed with checkpoint inhibitor plus chemotherapy combination treatment in lung cancer. This article is protected by copyright. All rights reserved.