Metabolic disease is highly complex involving multiple risk factors including obesity, hyperinsulinemia and insulin resistance as well as an ill-defined interplay between genetics, the environment and other factors. The mouse has become a work horse for many pre-clinical analyses of metabolic disease yet there are concerns about their applicability to humans and most studies are confined to single inbred strains. Here we provide a comprehensive metabolic analysis of a Diversity Outbred mouse population referred to here as DOz that displays profound genetic diversity. In contrast to many common inbred mouse strains, DOz mice displayed profound diversity in metabolic phenotypes even when fed healthy chow diet: 11% exhibited metabolically healthy obesity, 19% were obese with hyperinsulinemia, 5% were pre-diabetic, and 0.7% had type 2 diabetes (T2D). Exposure to a high fat diet (HFD) resulted in a profound shift in the majority of the population toward metabolic dysfunction concomitant with the emergence of metabolic disease. This contrasts with other studies using inbred strains indicating that the response of genetically diverse outbred populations is quite distinct to that seen in inbred mice. Finally, we use genetic mapping to identify loci associated with certain aspects of Metabolic Syndrome. These data suggest that this population possesses multiple risk alleles that contribute to the emergence of early metabolic disease risk factors in the absence of any dietary intervention. These findings emphasise the immense potential of Diversity Outbred mouse populations for dissecting the molecular and phenotypic character of metabolic disease.