We determined whether effects of neighborhood socioeconomic disadvantage on trajectories of aggression were moderated or mediated by neighborhood social organization and examined sex differences in neighborhood effects for rural adolescents. We used five waves of survey data collected over 2.5 years linked with neighborhood data from interviews with parents and the US Census. The sample (N = 5,118) was 50.1% female, 52.0% white and 38.3% African-American; average age at baseline was 13.1 years. Multilevel growth curve models for both girls and boys showed no significant interactions between neighborhood socioeconomic disadvantage and indicators of social organization. Neither sample showed evidence of mediated effects. In main effects models, neighborhood disadvantage was associated with the average aggression trajectory for girls. For boys, the effects of neighborhood socioeconomic disadvantage and social disorganization appeared to be confounded with each other. Neighborhood disadvantage is detrimental for rural girls regardless of the level of social organization.