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Background: The burden of multimorbidity has been observed worldwide and it has significant consequences on health outcomes. In Australia, health-related quality of life (HRQoL) is comparatively low amongst Aboriginal and/or Torres Strait Islanders, yet no studies have examined the effect of multimorbidity on HRQoL within this at-risk population. This study seeks to fill that gap by employing a longitudinal research design. Methods: Longitudinal data were derived from three waves (9, 13, and 17) of the household, income and labour dynamics in Australia (HILDA) Survey. A total of 1007 person-year observations from 592 Aboriginal and/or Torres Strait Islander individuals aged 15 years and above were included. HRQoL was captured using the 36-item Short-Form Health Survey (SF-36), and multimorbidity was defined using self-reports of having been diagnosed with two or more chronic health conditions. Symmetric fixed-effects linear regression models were used to assess how intraindividual changes in multimorbidity were associated with intraindividual changes in HRQoL. Results: Approximately 21% of Indigenous Australians were classified as experiencing multimorbidity. Respondents had statistically significantly lower HRQoL on the SF-36 sub-scales, summary measures, and health-utility index in those observations in which they experienced multimorbidity. Among others, multimorbidity was associated with lower scores on the SF-36 physical-component scale (β = − 6.527; Standard Error [SE] = 1.579), mental-component scale (β = − 3.765; SE = 1.590) and short-form six-dimension utility index (β = − 0.075; SE = 0.017). Conclusion: This study demonstrates that having multiple chronic conditions is statistically significantly associated with lower HRQoL amongst Indigenous Australians. These findings suggest that comprehensive and culturally sensitive health strategies addressing the complex needs of individuals with multimorbidity should be implemented to improve the HRQoL of Indigenous Australians. [ABSTRACT FROM AUTHOR]