Abstract Background The purpose of this study was to examine the relationship between the cancer health burden and themagnitude of work disability on cancer survivors in Australia from 2003 to 2017. Methods A longitudinal prospective study design was undertaken among cancer patients using data from the Household, Income and Labour Dynamics in Australia survey. The longitudinal effect was captured using a fixed effect multinomial logistic regression model, which predicted changes in the relationship between cancer burden and work disability level controlling for socio-demographic, lifestyle and life conditions predictors. Results The prevalence of long-term disability among cancer survivors was 50%, with 18% of patients experiencing extreme work disability. The magnitude of disability levels increased significantly with the level of health burden. Cancer survivors who faced a severe health burden were at 5.32 times significantly higher risk of having work disability compared with patients who had no health burden. Other potential predictors, such as older patients (relative risk ratio, RRR = 1.82; 95% CI: 1.57, 5.87), those engaged in lower levels of physical activities (RRR = 1.91; 95% CI: 1.07, 3.40), those who drink alcohol (RRR = 1.29; 95% CI: 1.15, 1.49), and poor socioeconomic status (RRR = 1.28; 95% CI: 1.16, 2.23) were all significantly associated with extreme work disability. Conclusion A substantial proportion of cancer survivors experienced work disability which was more pronounced with the magnitude of the cancer health burden. The different dimensions of disability might be prevented by introducing cancer survivor-specific evidence-based interventions, and incorporating comprehensive social support. Recommendations to improve public health policy aimed at reducing population-level unhealthy lifestyle behaviours include: using these findings to better outline the management of a sequelae course of treatment for cancer survivors; and identifying those who should undergo more intensive physical rehabilitation aimed at reducing their work disability level.