Background Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2). Methods In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1–49%, ≥ 50%, and unknown. Results The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups ( P  < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups ( P  = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1–49%, hazard ratio HR 0.19, 95% confidence interval CI 0.04–0.99, P  = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02–0.71, P  = 0.02; unknown, HR 0.30, 95% CI 0.08–1.22, P  = 0.09). Conclusions NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.