This paper addresses a validation study focusing on the process of adapting the EPOCH measure of adolescent well-being (Kern et al. in Psychol Assess 28(5):586–597. https://ifp.nyu.edu/?internalerror=true, 2016) to the school context and translating it into German—resulting in the EPOCH-School model (EPOCH-S) with the corresponding measure EPOCH-G-S (EPOCH-German-School). As schools represent an important context for promoting well-being, while at the same time, favorable effects of school-related well-being for adolescent development can be expected, research on school-related well-being is of utmost interest. To provide schools with the information they actually need to promote their students’ well-being, integrative measurements of school-related well-being are important. The EPOCH-G-S is a multidimensional approach to measuring students’ well-being in schools with five factors: Engagement, Perseverance, Optimism, Connectedness, and Happiness. Construct validity and convergent validity of the EPOCH-G-S measure were validated in this study with an Austrian student sample (grade 5 to 12) of N = 1651 students (52.03% males, 47.43% females, 0.55% others, mean age 13.13 years/ SD = 1.89). Validation results are in favor of the EPOCH-G-S as an instrument to assess students’ well-being in school. A second-order model was applied with well-being as a second-order factor and the five specific EPOCH first-order factors. This allows for detecting strengths and weaknesses in students’ well-being profiles and derive needs for intervention. Additional measurement invariance analyses regarding gender and age were conducted.