Sedentary behavior and screen‐based devices in particular have been negatively associated with a wide range of health and educational indicators. However, few have examined these relationships separately for school days and non‐school days, and none have used a person‐centered approach. This study aimed to identify school and non‐school day screen time profiles, as well as examine possible differences in health indicators (physical fitness, fatness, physical activity, sleep duration, and Mediterranean diet) and academic performance. This study involved the participation of 1573 Spanish adolescents aged 12–16 years (54.73% girls). Academic performance was measured through grades in Mathematics, Language, English, and Physical Education. Physical fitness was measured through a battery of tests (cardiorespiratory fitness was measured using the 20 m shuttle run test, and muscular strength with both handgrip and standing long jump tests), while fatness (skinfold thicknesses) was assessed with calipers. Finally, physical activity, screen time, sleep duration, and adherence to the Mediterranean diet were measured using self‐reported questionnaires. Hierarchical cluster analyses based on square Euclidian distances and Ward's method were performed based on daily minutes of screen time recorded on school and non‐school days. We identified four clusters labeled and described as: (1) “High‐high”: highest screen time on school and non‐school days; (2) “High‐low”: high screen time on school days and low screen time on non‐school days; (3) “Low‐high”: low screen time on school days and high screen time on non‐school days; (4) “Low‐low”: lowest screen time on school and non‐school days. Adolescents who belonged to the “High‐high” profile had worse health‐related behaviors (i.e., physical activity, sleep duration, and adherence to Mediterranean diet) and academic performance than most other profiles, while adolescents who belonged to “Low‐low” profile showed the opposite pattern. Adolescents in the “Low‐high” profile had a higher sleep duration on school days and better academic performance than those in the “High‐low” profile. No differences in body fat, cardiorespiratory fitness, and muscular strength were found between the four different profiles. The results suggest that adolescents who accumulated a large amount of screen time on school and non‐school days reported worse health‐related behaviors and academic performance. Moreover, adolescents who had high screen time on school days reported only a short sleep duration on school days and worse academic performance than on non‐school days. Conducting interventions to reduce screen time in these four profiles, particularly in the groups of students with more screen time on school days, becomes essential to improving adolescents' healthy lifestyles and academic performance.