Objectives: The present work aimed to measure the quality of life among adolescents in Abha City in southwestern Saudi Arabia. Methods: A descriptive cross-sectional study was performed targeting all male and female students enrolled in Abha secondary schools. The Arabic version of the World Health Organization Quality of Life Questionnaire (condensed edition) was used. Results: The study included 400 students. The reported average score of quality of life ranged from 60.6 for the physical health domain to 70.8 for the environmental domain. Factors that significantly affect the physical health domain were age, gender, nationality, mothers’ education, and monthly income. Regarding the psychological health domain, the significant determinants were age, gender, birth order, parental status, and income. As for the social relationship domain, the only significant factor was age. Regarding the environment domain, the significant determinants were birth order and income. Conclusion: The study augments evidence to boost relations between individual characters, lifestyle health behaviors, and quality of life among adolescents so that health managers, health instructors, and health advocates can create and execute relevant plans and services to specific groups to improve their quality of life.