This study integrates insights from social network analysis, activity space perspectives, and theories of urban and spatial processes to present an innovative approach to neighborhood effects on health-risk behavior among youth. We suggest spatial patterns of neighborhood residents’ non-home routine activities may be conceptualized as ecological, or “eco”-networks, which are two-mode networks that indirectly link residents through socio-spatial overlap in routine activities. We further argue structural configurations of eco-networks are consequential for youth’s behavioral health. In this study we focus on a key structural feature of eco-networks—the neighborhood-level extent to which households share two or more activity locations, or eco-network reinforcement—and its association with two dimensions of health-risk behavior, substance use and delinquency/sexual activity. Using geographic data on non-home routine activity locations among respondents from the Los Angeles Family and Neighborhood Survey (L.A.FANS), we constructed neighborhood-specific eco-networks by connecting sampled households to “activity clusters,” which are sets of spatially-proximate activity locations. We then measured eco-network reinforcement and examined its association with adolescent dimensions of health risk behavior employing a sample of 830 youth ages 12-17 nested in 65 census tracts. We also examined whether neighborhood-level social processes (collective efficacy and intergenerational closure) mediate the association between eco-network reinforcement and the outcomes considered. Results indicated eco-network reinforcement exhibits robust negative associations with both substance use and delinquency/sexual activity scales. Eco-network reinforcement effects were not explained by potential mediating variables. In addition to introducing a novel theoretical and empirical approach to neighborhood effects on youth, our findings highlight the importance of eco-network reinforcement for adolescent behavioral health.