Abstract Symptom severity and complexity have considerable impact on a patient’s cancer care journey. This study describes symptom scores of radiotherapy patients across their radiotherapy care trajectory and factors associated with symptom complexity. Patients who received radiotherapy at a single tertiary cancer center, who also completed at least one symptom-reporting questionnaire, the Edmonton Symptom Assessment Scale– Revised (ESAS-r) between October 1, 2019 and April 1, 2020 were included in this retrospective analysis. Symptom assessment time points were pre-treatment, start and end of radiation treatment and post-treatment follow-up. Mean ESAS-r scores for individual symptoms were descriptively analyzed by assessment timing and tumour group. We calculated a symptom complexity score for each ESAS-r measurement, using a validated algorithm, and assigned overall symptom complexity as low, moderate or severe. We modelled the association between assessment timing, and tumor group, with symptom complexity using Generalized Estimating Equations (GEE). The study cohort consisted of 1,632 patients who completed 2,519 ESAS-r questionnaires. Patients with lung and H&N cancers reported higher mean symptom scores compared to other tumour groups. Patients at the start of treatment had significantly lower odds of having a more severe symptom complexity, compared with patients pre-treatment (OR = 0.77, 95% CI = 0.64–0.93). Patients with H&N and lung cancer and patients prior to starting radiation may benefit most from increased symptom support and management.