PURPOSE: Cancer-related fatigue (CRF) is the most prevalent and distressing symptom among cancer patients and survivors. However, research on its prevalence and related disability in the post-treatment survivorship period remains limited. We sought to describe the occurrence of CRF within three time points in the post-treatment survivorship trajectory. METHODS: A self-administered mail-based questionnaire which included the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and the World Health Organisation Disability Assessment Schedule 2.0 was sent to three cohorts of disease-free breast, prostate or colorectal cancer survivors (6-18 months; 2-3 years; and 5-6 years post-treatment). Clinical information was extracted from chart review. Frequencies of significant fatigue by diagnostic group and time cohorts were studied and compared. Multivariate logistic regressions were conducted to examine the associations between CRF and demographic, clinical, and psychosocial variables. RESULTS: One thousand two hundred ninety-four questionnaire packages were returned (63 % response rate). A total of 29 % (95 % CI [27 % to 32 %]) of the sample reported significant fatigue (FACT-F ≤34), and this was associated with much higher levels of disability (p < 0.0001). Breast (40 % [35 % to 44 %]) and colorectal (33 % [27 % to 38 %]) cancer survivors had significantly higher rates of fatigue compared with the prostate group (17 % [14 % to 21 %]) (p < 0.0001). Fatigue levels did not differ between the three time cohorts. The main factors associated with CRF included physical symptom burden, depression, and co-morbidity (AUC, 0.919 [0.903 to 0.936]). CONCLUSIONS: Clinically relevant levels of CRF are present in approximately 1/3 of cancer survivors up to 6 years post-treatment, and this is associated with high levels of disability. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians need to be aware of the chronicity of CRF and assess for it routinely in medical practice. While there is no gold standard treatment, non-pharmacological interventions with established efficacy can reduce its severity and possibly minimize its disabling impact on patient functioning. Attention must be paid to the co-occurrence and need for possible treatment of depression and other co-occurring physical symptoms as contributing factors.