Aboriginal and Torres Strait Islander people experience high burden of cardiovascular, kidney and metabolic conditions, often manifesting in multimorbidity and contributing to over one third of life expectancy differentials. This article explores cardiovascular-kidney-metabolic (CKM) health within an Aboriginal cohort by documenting the burden of early risk, disease and factors associated with disease progression. A prospective longitudinal cohort of 601 Aboriginal people living in Central Australia spanning 2008-2016 was utilised. Research was driven by and based on community priorities and partnerships. Baseline data included questionnaires, clinical assessments and primary health care data; follow-up outcomes were derived from primary care clinical review, administrative hospitalisation and mortality datasets. Four percent of participants (mean: 41.3 years; 47% female) had no CKM risk factors (Stage 1 CKM Syndrome or greater) at baseline, 54.6% had established cardiovascular disease, chronic kidney disease, and/or diabetes mellitus. Greater presence of CKM disease and co/multimorbidity was associated with greater socioeconomic disadvantage. After adjusting for age, participants with co/multimorbidity were more likely to die during follow-up (hazard ratio [95% confidence interval]: 2.2 [1.1-4.3]) than participants without clinical disease at baseline. During a mean follow-up period of 6.8 years, 30.4% of participants living with no clinical disease at baseline developed at least one CKM condition, and 25% progressed to co/multimorbidity. This study reveals a higher prevalence of cardiovascular, kidney, and metabolic risk and disease than previously reported and compared to non-Indigenous counterparts. The health sector must recalibrate disease prevention, move beyond single-organ management and implement interdisciplinary care coordination to prevent expansion of inequities.