Objective: To examine the associations of physical activity (PA) and sitting time (sit) with cardio‐metabolic diseases. Methods: Cross‐sectional data from the Australian National Nutrition and Physical Activity Survey 2011-2012 (n=9,435) were used to classify adults into low and high risk groups based on their physical activity and sitting behaviour profiles. Logistic regression models examined associations between low and high risk classifications (high PA‐low sit; high PA‐high sit; low PA‐low sit; low PA‐high sit;) and socio‐demographic factors, and associations between low and high risk classifications and the prevalence of cardiovascular disease, Type 2 diabetes and metabolic syndrome. Results: These results characterise chronic disease risk based on both physical activity and sitting behaviour. Adults with the highest risk lifestyle behaviour pattern (low PA‐high sit) tended to be middle aged, male, at greater social disadvantage, smoke, report fair health, be abdominally obese and employed in administrative and driver occupations. These individuals had a substantially greater risk of cardiovascular disease and metabolic syndrome (OR=1.41, 95% CI 1.13, 1.75; OR= 2.37, 95% CI 1.63, 3.45, respectively). Conclusions: The findings highlight the importance of both sufficient physical activity and low sitting time for cardio‐metabolic health. Implications for public health: Primary prevention focus should consider physical activity and reduced sitting time as well as provision of relevant advice for cardio‐metabolic health.