In this study we examined the combined association of physical activity and sitting time with cardiometabolic risk factors in adults in Chile. This is a cross-sectional study based on 3201 adults aged from 18 to 98 years from the Chilean National Health Survey (2016–2017) who responded to the GPAQ questionnaire. Participants were considered inactive if spent < 600 METs-min/wk−1in physical activity. High sitting time was defined as ≥ 8 h/day. We classified participants into the following 4 groups: active and low sitting time; active and high sitting time; inactive and low sitting time; inactive and high sitting time. The cardiometabolic risk factors considered were metabolic syndrome, body mass index, waist circumference, total cholesterol, and triglycerides. Multivariable logistic regression models were performed. Overall, 16.1% were classified as inactive and high sitting time. Compared to active participants with low sitting time, both inactive participants with low (OR: 1.51; 95% CI 1.10, 1.92) and high sitting time (1.66; 1.10, 2.22) had higher body mass index. Similar results were found for high waist circumference: inactive participants with low (1.57; 1.14, 2.00) and high sitting time (1.84; 1.25, 2.43). We found no combined association of physical activity and sitting time with metabolic syndrome, total cholesterol, and triglycerides. These findings may be useful to inform programs focused on obesity prevention in Chile.