Amblyopia is an acquired defect due to a lack of visual stimulation. Self-efficacy is one of the factors affecting the quality of life (QoL) of individuals. Low self-efficacy can decrease cognitive and behavioral functioning, whereas increased self-efficacy leads to a change in treatment acceptance behavior and, subsequently, physical and mental health. This study aimed to determine the QoL and self-efficacy in adolescents with amblyopia. This descriptive cross-sectional study was performed on 300 patients referred to hospitals affiliated with Mashhad University of Medical Sciences, Iran, between 2015 and 2016. Data collection tools included: 1) demographic questionnaire, 2) general self-efficacy scale, and 3) WHO QoL questionnaire. Data were analyzed using SPSS software 24 using descriptive statistics. The results showed that the mean percentage in QoL was 45.43% (weak), and the mean score in self-efficacy was 21.66%, with a standard deviation of 8.10. There was also a positive and significant relationship between patients’ self-efficacy and QoL on each dimension. This study showed that demographic characteristics had no significant relationship with any of the variables of QoL and self-efficacy. However, data analysis showed a significant and positive relationship between self-efficacy and QoL.