This study tested whether childhood family instability is associated with mental health problems during adolescence through continued family instability and/or through a preadolescent onset of mental health problems. This test use data from a prospective population cohort of 2,230 Dutch adolescents (M age = 11.09, SD = 0.56 at the initial assessment). Childhood family instability was associated with both internalizing problems and externalizing problems during late adolescence. The association between childhood family instability and adolescent mental health problems largely disappeared when controlling for preadolescent onset of mental health problems but only slightly when controlling for continued family instability during adolescence. These patterns were comparable for both types of mental health problems but relatively stronger for internalizing problems. These results suggest that growing up in an unpredictable family environment has long-lasting negative mental health effects, most of which are due to a preadolescent onset of mental health problems.