Background: Amblyopia, when not diagnosed at appropriate age, leads to uncorrectable visual impairment with considerable social and financial implications. The aim of this study was to assess socio-demographic disparities in amblyopia prevalence among Israeli adolescents, in order to identify susceptible groups in the population. Methods: A nationwide, population-based, cross-sectional study of Israeli adolescents examined between 1993 and 2017. All study participants underwent visual acuity examination with socio-demographic data and previous medical history documented. Associations were analyzed using univariable and multivariable logistic regression models. Results: Among 1 334 650 Israeli-born candidates aged 17.15±0.26 years, amblyopia was diagnosed in 1.07%. The overall prevalence of amblyopia has declined from 1.59% in 1993 to 0.87% in 2017. Being in the lowest socioeconomic status and below average cognitive function scores increased the odds of amblyopia in both males [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.45-1.87; OR 1.27, 95% CI 1.19-1.35, respectively] and females (OR 1.61, 95% CI 1.30-1.98; OR 1.27, 95% CI 1.18-1.36, respectively). Among males, Orthodox and ultra-Orthodox educational systems were associated with increased odds of amblyopia (OR 1.16, 95% CI 1.09-1.25; OR 1.90, 95% CI 1.73-2.09). A significantly higher prevalence of amblyopia was recorded among 219 983 immigrants (1.51%, P<0.001). Conclusions: Although the overall prevalence of amblyopia has decreased during the observed years, we found substantial evidence of socio-demographic disparities in amblyopia prevalence among adolescents, suggesting disparities in the prevention of the disease and its treatment. Demonstration of inequities at a national level could aid future guidance of health policy and augment current vision screening programs.