Substance use is a frequently cited health risk behavior in the youth gang literature, yet little is known about how substance use patterns vary among gang-involved youth or the social ecological factors that contribute to potential variation. Developing relevant and effective service approaches will require an understanding of this variation and the malleable factors that are likely to promote or inhibit particular patterns of use. Using latent class analysis, we identified four substance use classes within a school-based sample of gang-involved youth (n = 2,770): Non-Users (38%), Past Users (15%), Casual Users (27%), and Frequent Multi-Users (21%). These classes were distinguished by substance type, frequency of use, and source of access. Demographic and substance use-specific ecological factors across the family, peer, school, and neighborhood contexts were found to significantly differentiate these classes. Specifically, acceptance of use by parents, friends, and neighbors, along with a lack of family rules and high accessibility in the neighborhood, significantly differentiated use patterns. Findings highlight the need for service approaches that are responsive to the unique needs of individuals and their environments. Implications for practice are discussed, including the potential utility of applying a harm reduction service framework to address youth gang substance use. [This paper was published in "Children and Youth Services Review" v119 2020.]