Type 2 diabetes mellitus (T2DM), cardiovascular disease, and chronic kidney disease are significant contributors to the 17-year disparity in life expectancy between Indigenous and non-Indigenous Australians. These three conditions are prevalent from a young age in Indigenous Australians and clearly contribute to their premature mortality. Risk factors that both exacerbate and promote these conditions include central obesity, dyslipidemia, cigarette smoking, albuminuria, inflammation, and poor socio-economic status. Although rates of screening for T2DM are higher in Indigenous Australians than in non-Indigenous Australians, gaps in clinical management of both T2DM and cardiovascular disease exist. To enhance survival and quality of life, prevention strategies are required at a population level and from a young age in Indigenous Australians.