Physical inactivity and high levels of screen time may negatively affect health-related quality of life (HRQoL) levels in children and adults. To analyze the associations between HRQoL and television (TV) viewing time adjusting for physical activity and weight status among school-age children. The study was conducted in Monteria, Colombia, with 546 students aged 11–18 years, from 14 randomly selected schools. HRQoL data was collected using the Pediatric Quality of Life Inventory (PedsQL). Students completed a self-reported questionnaire including items describing TV viewing time and physical activity. Associations between HRQoL and TV viewing time were explored using logistic regression models. Adjusted odds ratios (OR) showed that high TV viewing time (>2 hours/day) is significantly associated with low HRQoL [OR: 1.5; 95% confidence interval (CI): 1.0–2.2; p = 0.048], low psychosocial health (OR: 1.8; 95% CI: 1.2–2.5; p = 0.005), low emotional functioning (OR: 1.9; 95% CI: 1.4–2.6; p = 0.001), low social functioning (OR: 1.4; 95% CI: 1.0–1.9; p = 0.046), and low school functioning (OR: 1.5; 95% CI: 1.1–2.2; p = 0.025). This study provides evidence of significant associations between high TV viewing time and poor HRQoL among school-age children from Monteria, Colombia, which were independent of physical activity and weight.