Asthma imposes a significant social burden on children, their families, and society at large. As a chronic health condition, effective management could greatly benefit from consistent adherence to guidelines. Despite this, minimal effort has been exerted to examine the impact of asthma management guidelines and adherence to treatment on children with asthma and the mothers caring for them. This study was designed to evaluate the influence of asthma management guidelines on the knowledge and treatment adherence among children with asthma and their mothers. A quasi-experimental design was utilized, and the study was conducted at two large hospitals in Jordan: Princess Rahma Hospital and King Hussein Medical Center. A purposive sample of children aged 6–12 years (n= 100) who were accompanied by their mothers (n= 100) were recruited for this study. Data were collected using a structured questionnaire and an observation checklist before and after the implementation of guidelines. Statistical analyses were performed using SPSS. The results revealed a statistically significant improvement in knowledge related to asthma among children and their mothers (p< 0.001). Additionally, a statistically significant difference was observed in the children’s adherence to their treatment regimen before and after the implementation of asthma management guidelines (p< 0.001). Moreover, the improvements in knowledge and practice related to asthma were sustained in the follow-up assessments. In conclusion, the guidelines had a beneficial effect on the children’s adherence to their treatment regimen both before and after their implementation. Thus, asthma patients should adhere to conventional guidelines at various health services to manage their condition effectively.