The aim of this study was to investigate the association between physical activity (PA), both occupational (OPA) and during leisure time (LTPA), with obesity and cardiovascular risk factors in Chilean adults. 5,157 participants from the Chilean National Health Survey 2009–2010 were included in this study. OPA and LTPA levels were assessed using the Global Physical Activity Questionnaire. The association between both PA with obesity and cardiovascular risk factors was determined using logistic regression. Our findings showed a significant trend between higher LTPA and lower odds for obesity (OR 0.64 [95% CI: 0.53; 0.76], central obesity 0.52 [0.44; 0.61]) and other cardiovascular risk factors including diabetes (OR: 0.72 [0.55; 0.94]), hypertension (OR: 0.59 [0.50; 0.71]) and metabolic syndrome (OR: 0.62 [0.50; 0.78]). In contrast, OPA was only associated with lower odds of diabetes (OR: 0.79 [0.65; 0.98]) and hypertension (0.85 [0.74; 0.98]). In conclusion, LTPA was associated with a lower risk of all major cardiovascular risk factors, whereas OPA was only associated with a lower risk of diabetes and hypertension.