Australian Indigenous young people have a 10-fold excess of deaths from ischaemic heart disease compared with non-Indigenous Australians, yet the reasons behind this remain understudied. This paper aims to describe cardio-metabolic profiles among Australian Indigenous (n = 459) and non-Indigenous (n = 117) young adults (21–27 years). The association between body size and an adverse cardio-metabolic profile (≥3 abnormal cardio-metabolic markers) is assessed by gender and urban/rural residence, employing regression analyses. The prevalence of obesity was highest among urban Indigenous participants, both males and females (22% and 23%, respectively). Overall, BMI showed a significant positive association with an adverse cardio-metabolic profile. Moreover, adverse cardio-metabolic profile was present in a substantial proportion of Indigenous participants even in overweight and normal BMI categories. Among females, this could reflect elevated waist circumference, which was present in half of those of normal weight. Remote Indigenous females had the highest predicted probability of having an adverse cardio-metabolic profile across all BMI categories (13% for underweight, 54% for normal BMI, 93% for overweight, and 99% for obese). Our findings highlight the associations between obesity and adverse cardio-metabolic profiles among Indigenous and non-Indigenous youth. Culturally-relevant strategies that address lifestyle risks, including access to healthy food, are urgently needed in this age group.