Objective: To determine the association between screen time and physical activity with quality of life among Chilean university students. Methods: Cross-sectional and analytical study conducted on 726 first-year university students who replied three questionnaires: Youth Risk Behavior Survey, WHO Quality of Life-BREF scale, and the International Physical Activity Questionnaire. Results: There were differences in overall quality of life (p < 0.001) and level of satisfaction in health (p < 0.01) according to screen exposure time. These results follow a linear trend for all the quality of life domains (p < 0.01), and they indicate that there is an inverse association between screen time and quality of life. Conclusion: There is an inverse association between screen time and quality of life in university students. Students with a longer screen exposure time showed a lower quality of life, specifically in the domains of social relationships and psychological health, regardless of sex, physical activity, or socioeconomic level.