<p>Oral mucositis is a debilitating adverse effect of radiotherapy in head and neck cancer. It progresses from erythema to painful ulcerations, often causing infections, nutritional impairment, treatment interruption, and reduced survival. While treatment-related factors are well established, patient-related risk determinants remain insufficiently defined. Thus, this study investigated the association between the onset and peak severity of radiation-induced oral mucositis in patients with head and neck cancer and their clinicopathological, biobehavioral, and demographic characteristics. To carry out this study, patients diagnosed with head and neck cancer and undergoing mandatory radiotherapy treatment were recruited. Fifty patients undergoing radiotherapy were evaluated daily. The analysis focused on the onset and peak severity of oral mucositis. Chemotherapy was significantly associated (<i>P</i> = 0.034) with earlier oral mucositis onset. Diabetes (<i>P</i> = 0.017) and radiation dermatitis (<i>P</i> = 0.017) were statistically associated with the severity of mucositis at the time of onset, while hypertension (<i>P</i> = 0.030), diabetes (<i>P</i> = 0.016), mild and moderate alcohol consumption (<i>P</i> = 0.029), radiation dermatitis (<i>P</i> = 0.001), odynophagia (<i>P</i> = 0.022), burning mouth (<i>P</i> = 0.003), difficulty with hygiene (<i>P</i> = 0.020), and use of opioids (<i>P</i> = 0.045) were associated with the most severe degrees at the peak of lesion. Severe smokers were associated with a greater occurrence of mucositis lesions in the lip region at two times. This study demonstrated that the interaction between clinicopathological and biobehavioral factors exhibits distinct patterns depending on the stage of oral mucositis progression. A comprehensive understanding of these complex relationships is crucial for developing targeted strategies to prevent severe mucositis and optimize treatment outcomes.</p>