Youth interpersonal firearm violence disproportionately affects Black youth, with residential racial segregation as a key determinant. Racially segregated neighborhoods, which are economically isolated (e.g., neighborhood disadvantage), are linked to increased exposure to violence. This exposure, in turn, is a determinant of youth firearm aggression (i.e., using a gun on someone else). Mechanisms from residential racial segregation to firearm aggression, however, have not been evaluated. Therefore, we tested neighborhood disadvantage and exposure to violence as mediators in the association between residential racial segregation and youth firearm aggression. Participants were 338 Black youth who had used drugs in the past 6 months and sought care in an urban emergency department. Using serial mediation analysis, residential racial segregation was indirectly associated with youth firearm aggression via neighborhood disadvantage and then exposure to violence. While researchers have documented the association between structural racism and firearm violence injury and incidents, our study assessed multiple socioecological mechanisms simultaneously. Identifying the downstream socioecological consequences of residential segregation can guide the development of firearm aggression prevention programs addressing the consequences of racism.