This multi-center retrospective study aimed to evaluate the safety and efficacy of first-line immunotherapy in non-small-cell lung cancer (NSCLC) patients with brain metastases (BM). The study included 138 patients treated with immune checkpoint inhibitors (ICIs), either alone or in combination with brain radiotherapy (BRT), from 2020 to October 2023. Intracranial overall response rate (iORR), overall response rate (ORR), progression-free survival (PFS), intracranial progression-free survival (iPFS), overall survival (OS) and treatment-related toxicities were evaluated. Although patients receiving ICIs plus BRT showed a trend toward longer OS compared with ICI alone, the difference was not statistically significant (P = 0.201). Among 82 patients with available data, the iORR was 49.1% (35-63) in the ICIs alone group, and 75.9% (56-90) in the ICIs + BRT group. Notably, in patients requiring corticosteroids or mannitol, combination therapy was associated with a better prognosis (P = 0.05). We found that the iORR of patients treated with ICIs + BRT was improved and did not increase the incidence of serious adverse events (SAEs). Besides, the combination of ICIs and BRT improved the survival rate of subgroups of patients using corticosteroids.