<p>This study aims to investigate the relationships between screen-based sedentary behavior, emotional eating, physical activity, and physical and mental health of university students. A structured questionnaire survey was randomly administered to 1800 university students from three universities in Southwestern China. The survey collected self-reported data using the Screen Time Scale, Physical Activity Rating Scale-3, Dutch Eating Behavior Questionnaire–Emotional Eating subscale, and Global Physical and Mental Health Scale. SPSS 26.0 was used to analyze the relationships among these factors and physical and mental health. The results showed that screen-based sedentary behavior was significantly negatively associated with physical and mental health (<i>β</i> = −0.282, <i>p</i> &lt; 0.001). Emotional eating was significantly associated with the relationship between screen-based sedentary behavior and physical and mental health, with the indirect effect accounting for 39.296% of the total effect. Additionally, physical activity moderated this relationship (<i>β</i> = 0.002, <i>p</i> &lt; 0.01). These findings highlight the significant association between physical activity, a healthy lifestyle, and university students’ overall well-being, offering new insights for both theoretical research and practical interventions.</p>