Researchers have reported that network characteristics are associated with substance use behavior. Considering that social interactions within online networks are increasingly common, we examined the relationship between online network characteristics and substance use in a sample of emerging adults (ages 18–24) from across the United States (N = 2,153; M = 21 years old; 47 % female; 70 % White). We used regression analyses to examine the relationship between online ego network characteristics (i.e., characteristics of individuals directly related to the focal participant plus the relationships shared among individuals within the online network) and alcohol use and substance use, respectively. Alcohol use was associated with network density (i.e., interconnectedness between individuals in a network), total number of peer ties, and a greater proportion of emotionally close ties. In sex-stratified models, density was related to alcohol use for males but not females. Drug use was associated with an increased number of peer ties, and the increased proportion of network members’ discussion and acceptance of drug use, respectively. We also found that online network density and total numbers of ties were associated with more personal drug use for males but not females. Conversely, we noted that social norms were related to increased drug use and this relationship was stronger for females than males. We discuss the implications of our findings for substance use and online network research.