The main purpose of this study was to examine the relationships between school-based sedentary behavior, physical activity, and health-related outcomes, including cardiorespiratory fitness, weight status, and health-related quality of life (HRQOL) among Hispanic children. The participants were 374 children (192 boys, 182 girls / Mage = 9.64) recruited from four elementary schools from 3rd grade through to 5th grade. Sedentary behavior and physical activity behaviors (light physical activity [LPA] and moderate-to-vigorous physical activity (MVPA)) during school were measured by accelerometers. Cardiorespiratory fitness and weight status were measured using the FITNESSGRAM®, while HRQOL was measured using the PedsQL 4.0TM Spanish version, a validated questionnaire. Sedentary behavior was negatively correlated with cardiorespiratory fitness and HRQOL but positively associated with weight status. MVPA was positively correlated with cardiorespiratory fitness and HRQOL, but negatively associated with weight status and sedentary behavior. Multiple regressions demonstrated that sedentary behavior significantly predicted cardiorespiratory fitness and weight status, whereas MVPA significantly predicted HRQOL. With the current public health priority aiming to reduce health disparities in minority populations, the findings of this study provide important insights. Educators, health care providers, or other professionals working with Hispanic children are encouraged to focus on reducing sedentary behavior and promoting physical activity to improve their health-related outcomes.