Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3–18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53–0.84; Harmonized criteria), obesity (BMI > 30 kg/m², RR = 0.76;CI95% = 0.59–0.98), high waist circumference (RR = 0.82;CI95% = 0.69–0.98), and high triglyceride (RR = 0.60;CI95% = 0.47–0.75), insulin (RR = 0.58;CI95% = 0.46–0.74) and glucose (RR = 0.77;CI95% = 0.62–0.96) concentrations as well as low high-density lipoprotein cholesterol (HDL―C) concentration (RR = 0.78;CI95% = 0.66–0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk.