Background: Commonly used first-line (1L) chemotherapies for patients with advanced squamous-cell lung cancer (SCC) include gemcitabine–platinum (GP), nab-paclitaxel–carboplatin (nabpc), and sb-paclitaxel–carboplatin (sbpc) regimens. However, no head-to-head trials have compared those treatments. In the present study, we compared the efficacy of 1L GP, nabpc, and sbpc in patients with SCC and in patients with SCC who subsequently received second-line (2L) immunotherapy. Methods: Medical records of patients who initiated the 1L treatments of interest between June 2014 and October 2015 were reviewed by 132 participating physicians. Kaplan–Meier curves were used to evaluate overall survival (os), progression-free survival (PFS), and treatment discontinuation (TD), and then Cox proportional hazards regression was used to compare the results between the cohorts. Results: Medical records of 458 patients with SCC receiving GP (n = 139), nabpc (n = 159), or sbpc (n = 160) as 1L therapy were reviewed. Median os was longer with nabpc (23.9 months) than with GP (16.9 months; adjusted hazard ratio vs. nabpc: 1.55; p < 0.05) and with sbpc (18.3 months; adjusted hazard ratio: 1.42; p = 0.10). No differences were observed in PFS (median PFS: 8.8, 8.0, and 7.6 months for GP, nabpc, and sbpc respectively; log-rank p = 0.76) or in TD (median TD: 5.5, 5.7, and 4.6 months respectively; p = 0.65). For patients who subsequently received 2L immunotherapy, no differences in os were observed (median os: 27.3, 25.0, and 23.0 months respectively; p = 0.59). Conclusions: In a nationwide sample of SCC patients, longer median os was associated with 1L nabpc than with GP and sbpc. Median os for all 1L agents considered was similar in the subgroup of patients who sequenced to a 2L immunotherapy.