Methods: Homeless youth aged 13–24 were randomly sampled from 41 service and street sites in Los Angeles County (N = 419). Predictors of substance use were examined using linear regression analysis (for average number of drinks and average number of cigarettes per day) and negative binomial regression analysis (for frequency of past month marijuana use). Results: Youth with more substance users in their networks reported greater alcohol, cigarette, and marijuana consumption regardless of whether these network members provided tangible or emotional support. Marijuana use was more frequent for youth who met more network members through homeless settings, but less frequent among those who met more network members through treatment or AA/NA. Greater alcohol use occurred among youth who met more network members through substance use-related activities. Youth having more adults in positions of responsibility in their networks consumed less alcohol, and those with more school attendees in their networks consumed less alcohol and cigarettes. Conclusions: Findings highlight the importance of social context in understanding substance use among homeless youth. Results also support the relevance of network-based interventions to change social context for substance-using youth, in terms of both enhancing pro-social influences and reducing exposure to substance use.