Objectives The project is designed to compare the clinical efficacy and adverse events resulting from immune checkpoint inhibitors (ICIs) plus chemotherapy and chemotherapy alone in patients with small cell lung cancer (SCLC). Methods PubMed Database and ClinicalTrials.gov were both searched to identify randomized controlled clinical trials for assessing ICIs in all-stage SCLC. After screening in strict accordance with the inclusion and exclusion criteria, eligible studies were evaluated in regard to the population, intervention, comparator, outcome as well as study design (PICOS) pattern. Furthermore, primary endpoints of these randomized controlled trials (RCTs) included overall survival (OS), progression-free survival (PFS) and complete/objective response rate (CRR/ORR). Statistical analyses were realized via Review Manager Version 5.3 Software. Results Compared with the chemotherapy alone group, the ICIs plus chemotherapy group significantly improved with respect to such indicators as OS (hazard ratio (HR) = 0.82, 95% CI 0.74-0.90, P < 0.0001), PFS (HR = 0.80, 95% CI 0.74-0.87, P < 0.00001) and ORR (64.7% versus 59.1%). According to the safety analysis, the incidence of treatment-related adverse events (trAEs) at all grades was higher in ICIs plus chemotherapy group (OR = 1.59, 95% CI 1.20-2.10, P = 0.001), bearing no statistical significance at grade 3 or above (OR = 1.21, 95% CI 0.99-1.49, P = 0.07). Conclusions The combination of ICIs and chemotherapy witnessed better anti-neoplastic efficacy for SCLC. Moreover, the incidence of trAEs at all grades was elevated in ICIs plus chemotherapy group, with little discrepancy in both groups at grade 3 or above.