This study tested whether life history strategy (LHS) and its intergenerational transmission could explain young adult use of common psychoactive substances. We tested a sequential structural equation model using data from the National Longitudinal Survey of Youth. During young adulthood, fast LHS explained 61% of the variance in overall liability for substance use. Faster parent LHS predicted poorer health and lesser alcohol use, greater neuroticism and cigarette smoking, but did not predict fast LHS or overall liability for substance use among young adults. Young adult neuroticism was independent of substance use controlling for fast LHS. The surprising finding of independence between parent and child LHS casts some uncertainty upon the identity of the parent and child LHS variables. Fast LHS may be the primary driver of young adult use of common psychoactive substances. However, it is possible that the young adult fast LHS variable is better defined as young adult mating competition. We discuss our findings in depth, chart out some intriguing new directions for life history research that may clarify the dimensionality of LHS and its mediation of the intergenerational transmission of substance use, and discuss implications for substance abuse prevention and treatment.