Background: Asthma is identified as the most prevalent chronic non-communicable childhood illness at any age worldwide, mainly affecting health, functioning, and pediatric quality of life (PedsQL) dimensions in children. Objectives: The current study aimed to evaluate the status of the PedsQL in asthmatic children versus healthy controls for the ultimate goal of developing childhood asthma community-based integrated preventive and management programs. Methods: This analytic cross‐sectional study was carried out on 96 children participants with asthma and 95 healthy children, aged eight to twelve years, from January to December 2019. The different aspects of quality of life (QoL) and demographic characteristics of all subjects with the same age and gender were examined using the standardized disease-specific PedsQL questionnaire (consisting of 23 items) and the personal information questionnaire, respectively. The P < 0.05 criterion was set as the significance threshold. Results: The outcomes of patients’ responses associated with the PedsQL subscale showed significantly lower mean scores in children with controlled asthma compared to healthy children (P < 0.001). This model covered physical, emotional (significantly lower mean scores), psychological, and social effects in addition to school functions, showing statistically significant differences between the two groups (P < 0.001). In contrast to physical and school-related activities, lesser social status, emotional characteristics, and an overall score of QoL were significantly associated with poor QoL in lower-income children (P < 0.001). No significant difference was found between the two groups regarding sex, maternal educational level, or family income, but the two groups were significantly different in terms of paternal educational level and smoking (P < 0.05). Conclusions: It was found that asthma had profound unfavorable effects on patients’ healthy lifestyles and activities, mostly concerning daily physical activities, socio-emotional functioning, intellectual performance, school productivity, and psychological harmonization.