Objectives: To assess associations, both individually and in combination, between leisure-time physical activity and sedentary behavior, and cardiometabolic health. Methods: This cross-sectional study included 13,931 civil servants participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Leisure-time physical activity was analyzed using the leisure-time domain of the long-form International Physical Activity Questionnaire, while questions related to cumulative sitting time and leisure-based screen time on a weekday and on one day on the weekend were used to establish sedentary behavior. Data analysis was performed using multivariate logistic regression. Results: Following adjustment for confounding variables, high levels of leisure-time physical activity and low levels of sedentary behavior were both associated with favorable cardiometabolic health markers in both genders. When these two factors were analyzed in conjunction, taking the combination of low levels of leisure-time physical activity and high levels of sedentary behavior as the reference, the inverse associations with cardiometabolic variables became even more significant. Conclusion: High levels of leisure-time physical activity and low levels of sedentary behavior were both inversely associated with the cardiometabolic variables analyzed; however, the two variables when evaluated in conjunction appear to produce more consistent associations, particularly when sedentary behavior is evaluated according to leisure-based screen time.