Immunotherapy combined with chemotherapy has recently changed the first-line treatment of several cancers. We performed a systematic review and meta-analysis to assess the efficacy and safety of programmed cell death 1 (PD-1) inhibitor plus chemotherapy as a first-line treatment for advanced esophageal cancer. Data were collected from eligible studies searched from PubMed, Web of Science, Cochrane Library, Embase, and meeting abstracts. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and the pooled odds ratios (ORs) for objective response rate and treatment-related adverse events (TRAEs) were estimated to assess the efficacy and safety of PD-1 inhibitor plus chemotherapy versus chemotherapy. We performed several subgroup analyses to explore the variables affecting immunotherapy efficacy in esophageal cancer. The 5-point Jadad scoring system, the bias risk assessment and sensitivity analyses were used to evaluate the quality of the meta-analysis. Compared with the chemotherapy group, the OS (HR=0.70; P<0.01) and PFS (HR=0.62; P<0.01) were significantly longer and the objective response rate (OR=2.07; P<0.01) was significantly higher in the PD-1 inhibitor plus chemotherapy group. An OS benefit was observed in patients regardless of histology or programmed cell death 1 ligand 1 combined positive score. OS and PFS were generally consistent across subgroups by clinical features. In safety analyses, PD-1 inhibitor plus chemotherapy had a significantly higher incidence of TRAEs (OR=1.85; P<0.01), but there was no significant difference in grade 3 or higher TRAEs (OR=1.24; P=0.05). Compared with chemotherapy, PD-1 inhibitor plus chemotherapy improves antitumor activity and controllable adverse events in the first-line treatment of advanced esophageal cancer.