This study aimed to identify homeless youths’ lifestyle and trauma-related risk factors as well as protective factors associated with alcohol use disorder or no disorder and drug use disorder or no disorder. Youth receiving homeless services in Denver (n = 201), Austin (n = 200), and Los Angeles (n = 200; N = 601) completed quantitative interviews assessing demographic information, alcohol and drug use, homeless lifestyle risk factors, trauma-related risk factors, and protective factors. Findings showed differences in trauma-related risk factors between alcohol and drug use disorders, but not homeless lifestyle risks. Protective factors predicted substance use disorders beyond risk factors. Understanding trauma-related risk and protective factors associated with substance use disorders could improve interventions.