Navigating between cultures in addition to developmental changes and challenges in early adolescence can be difficult. We investigated school, family, and ethnic group as conditions for acculturation and school adjustment among early-adolescent boys and girls. Analyses were based on 860 mostly second- and third-generation immigrant students from 71 countries (50% male; M_age = 11.59 years), attending German secondary schools. Perceived support for inclusion and integration in school and family were associated with a stronger orientation toward both cultures (integration) and better adjustment (e.g., higher school marks, more well-being). Perceived cultural distance and ethnic discrimination were associated with a stronger ethnic and weaker mainstream orientation (separation), and lower adjustment. Boys perceived contextual conditions more negatively, had a weaker mainstream orientation, and showed more behavioral problems but did not differ from girls in the associations between contextual conditions and acculturation and adjustment. Implications for research, policy, and practice are discussed.