Early adolescence represents a particularly sensitive period in the life of young learners, which is accompanied by an increase in school alienation. Due to its harmful nature (Hascher and Hadjar in Educ Res 60:171-188, 2018. 10.1080/00131881.2018.1443021), school alienation may lead to unfavorable consequences such as low academic achievement (Johnson in J Educ Technol Soc 8:179-189, 2005; Reinke and Herman in Psychol Schools 39:549-559, 2002). This study investigates the longitudinal relationship between school alienation domains, namely alienation from learning, from teachers, and from classmates, and academic achievement among secondary school students of grade 7 to grade 9 in Switzerland and Luxembourg. Data were collected from 403 students in the Swiss canton of Bern and 387 students in Luxembourg who participated in three waves of the “School Alienation in Switzerland and Luxembourg (SASAL)” research project. Cross-lagged modeling was applied to examine the correlations between school alienation domains and academic achievement at each of the three time points, the temporal stability of school alienation domains and academic achievement, and their cross-lagged effects across time, controlling for students’ gender, school track, parental occupational status, and migration background. Results show that the pattern of relationships is defined by the school alienation domain and the cultural context, pointing to the complex interplay between the multidimensional construct of school alienation and academic outcomes of secondary school students.