Purpose: Addressing substance abuse in rural America requires extending our understanding beyond urban-rural comparisons to how substance abuse varies across rural communities of different sizes. We address this gap by examining substance abuse prevalence across 4 geographic levels, focusing on youth (age 12-17 years) and young adults (age 18-25 years). Methods: The analysis is based on 3 years (2002-2004) of pooled data from the National Survey on Drug Use and Health. We measure rurality using a four-tier consolidation of the 2003 Rural-Urban Continuum Codes: urban, rural-adjacent, rural-large, and rural-small and medium. Findings: Rural youth have higher alcohol use and methamphetamine use than urban youth and the more rural the area, the higher the use. Rural young adults living in rural-large areas have higher rates of substance abuse than their urban peers; those living in the most rural areas have nearly twice the rate of methamphetamine use as urban young adults. Rural youth are more likely than urban youth to have engaged in the high-risk behavior of driving under the influence of alcohol or other illicit drugs. Conclusions: Higher prevalence rates, coupled with high-risk behavior, place rural youth and young adults at risk of continued substance use and problems associated with this use. Rural community infrastructure should be enhanced to support substance abuse prevention and intervention for these populations.