Aims: Low-dose weekly cisplatin with concurrent radiotherapy (wCRT) has been proposed as a less toxic alternative to the current standard of high-dose three-weekly cisplatin with concurrent RT (twCRT) for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC); however, its efficacy and safety remain controversial. This study aimed to investigate the efficacy and safety of wCRT for LA-HNSCC treatment. Methodology: We retrospectively analyzed consecutive patients with stage III or IV LA-HNSCC who underwent definitive wCRT as the first-line treatment between January 2007 and December 2021 at a single institution. Patients with distant metastases or p16-positive oropharyngeal cancer or who had undergone induction chemotherapy were excluded. Cisplatin (40 mg/m²) was administered weekly with concurrent radiotherapy (66–70 Gy). Overall survival (OS), progression-free survival (PFS), response rates, and adverse events were evaluated. Prognostic factors were analyzed using Cox regression models. Results: Seventy-eight eligible patients were identified, 32 (41.0%) of whom were aged ≥70 years. The 2- and 5-year overall survival (OS) rates were 81.0% and 63.5%, respectively, with a complete response rate of 89.7%. The 2- and 5-year PFS rates were 62.3% and 51.2%, respectively. A cumulative cisplatin dose ≥200 mg/m² was achieved in 88.5% of patients and was the only independent prognostic factor for OS (hazard ratio 0.32, 95% confidence interval 0.11–0.88, p=0.02). Acute adverse events were generally manageable, with fewer non-haematological toxicities. Conclusion: Definitive wCRT demonstrated favorable survival outcomes with acceptable toxicity in patients with LA-HNSCC. Achieving a cumulative cisplatin dose ≥200 mg/m² was significantly associated with improved survival, suggesting its importance as a therapeutic target. wCRT may be a viable alternative to standard high-dose regimens, particularly in selected patients.