Purpose: Health-related quality of life (HRQoL) and associated factors were assessed among 155 Indigenous Australian adult cancer patients 6 months post-diagnosis. Methods: The Assessment of Quality of Life-4D Questionnaire was used to assess HRQoL. Differences in the median utility score among subgroups of interest were examined using nonparametric tests. Factors associated with excellent HRQoL were assessed through logistic regression. Results: Participants’ mean age was 52 years (range 20–78), and the majority were female (60 %), unemployed (72 %), and recruited from outpatients clinics (64 %). Breast cancer (27 %) was the most common diagnosis. The median HRQoL score was 0.62; 14 % of participants reported excellent HRQoL (>0.90). After adjusting for age, admission status, and treatment, excellent HRQoL was more likely among participants of Torres Strait Islander origin [adjusted odds ratio (AOR) 3.68; 95 % CI 1.23–11.01], those living in regional areas (AOR 5.59; 95 % CI 1.42–22.06), and those whose main language spoken at home was not English (AOR 3.60; 95 % CI 1.08–11.99) and less likely among those reporting less contact with Indigenous people (AOR 0.23; 95 % CI 0.68–0.81). Conclusion: Assessing HRQoL is important to identifying and improving the length and quality of cancer survivorship, especially in groups that have significantly poorer cancer outcomes, such as Indigenous Australians. Acknowledging the study’s observational nature, we found HRQoL was lower than reported for other Australians, and we identified some socio-demographic factors that were associated with excellent HRQoL. Such assessments are an important component of identifying and evaluating appropriate interventions to improve the health and well-being of Indigenous cancer patients.