Evidence suggests age and sex differences in risk factors for chronic disease. This study examined lifestyle and biomedical risk factors among men (m) and women (w) in early-middle (25⁻51 years), middle (52⁻64) and older (65+) adulthood. Cross-sectional data from the 2011⁻2012 Australian Health Survey (n = 3024) were analysed. Self-reported dietary, activity, sleep behaviours and collected biomedical data were analysed. Early-middle adults failed to meet fruit, vegetable (95.3%) and sugar-sweetened beverage (SSB, 34.9%) recommendations. Older adults had higher prevalence of overweight/obesity (70%), high blood pressure (38.0%) and fewer met physical activity guidelines (36.3%). Prior to older adulthood, more men consumed SSBs (early-middle m 45.6%, w 24.4%; middle m 26.0%, w 19.3%), and fewer met sedentary behaviour recommendations (early-middle m 43.2%, w 62.1%; middle m 46.4%, w 63.9%). Differences in overweight/obese women in early-middle (44.8%) to middle adulthood (64.7%) were significant. Biomedical risk was greatest in middle age; abnormal cholesterol/lipids increased specifically for women (total cholesterol early-middle 24.9% middle 56.4%; abnormal LDL-cholesterol early-middle 23.1% middle 53.9%). Adherence to lifestyle guidelines was low; particularly among men. While men exhibited greater clinical risk overall, this significantly increased among women in middle-adulthood. Public health strategies to improve lifestyle, monitor and intervene among middle-aged women are warranted.