Background This study aimed to analyze the clinical outcomes associated with patients with recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC) who received cetuximab-based chemotherapy in a real-world clinical setting. Methods Clinical data were extracted from RM HNSCC patients diagnosed between 2016 and 2019. Kaplan–Meier survival estimates and Cox proportional hazards model were used for survival analyses. Results Of 106 RM HNSCC patients (mean age = 55.1 years), 38.7% exhibited recurrent disease and 61.3% had metastatic disease. The majority of patients showed a habit of addictive substance use, including alcohol (67.0%), betel nuts (71.7%), or tobacco (74.5%). The primary tumor sites included the oral cavity (64.1%), hypopharynx (19.8%), and oropharynx (16.0%). The median number of cetuximab cycles for the 106 patients was 11 (2–24). The disease control rate (DCR) was 48.1%, and the overall response rate (ORR) was 28.3%. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 9.23 months, respectively. Patients treated with more than 11 cycles of cetuximab exhibited a longer median PFS and median OS than did patients treated with less than 11 cycles (median PFS: 7.0 vs. 3.0 months, p < 0.001; OS: 12.43 vs. 4.46 months, p = 0.001). Patients without previous concurrent chemoradiotherapy (CRT) had a better median PFS than did those with previous CRT (6.0 vs. 4.0 months, p = 0.046). Multivariable analysis revealed that perineural invasion and fewer cycles of cetuximab (<11 cycles) were independent risk factors associated with disease progression. In addition, the reduction in treatment cycles of cetuximab and advanced lymph node metastasis were independent prognostic factors predicting poorer overall survival. Conclusion Our study provides important real-world data regarding cetuximab-containing treatment in RM HNSCC. Consistent administration of cetuximab could be associated with more favorable outcomes in RM HNSCC in endemic carcinogen exposure areas.