Background Few studies assess whether place characteristics are associated with social network characteristics that create vulnerability to substance use. Methods This longitudinal study analyzed 7 waves of data (2009-2014) from a predominantly substance-using cohort of 172 African-American adults relocated from public housing complexes in Atlanta, GA, to determine whether post-relocation changes in exposure to neighborhood conditions were associated with four network characteristics related to substance use: number of social network members who used illicit drugs or alcohol in excess in the past six months (“drug/alcohol network”), drug/alcohol network stability, and turnover into and out of drug/alcohol networks. Individual-and network-level characteristics were captured via survey and administrative data were used to describe census tracts where participants lived. Multilevel models were used to assess relationships of census tract-level characteristics to network outcomes over time. Results On average, participants relocated to census tracts that had less economic disadvantage, social disorder, and renter-occupied housing. Post-relocation reductions in exposure to economic disadvantage were associated with fewer drug/alcohol network members and less turnover into drug/alcohol networks. Post-relocation improvements in exposure to multiple census tract-level social conditions were associated with fewer drug/alcohol network members, less turnover into drug/alcohol networks, less drug/alcohol network stability, and more turnover out of drug/alcohol networks. Conclusion Relocating to neighborhoods with less economic disadvantage and better social conditions may weaken relationships with substance-using individuals.