Previous research indicates that adverse childhood experiences (ACEs) increase the risk for illicit drug use. Yet, much of this research relies on retrospective ACE reports and does not consider the wide array of more proximal life experiences that may impact adults’ substance use. The present research used two waves of data from the longitudinal Toledo Adolescent Relationships Study (TARS) to examine the impact of ACEs reported during adolescence on illicit drug use frequency in adulthood (average age 32) among 930 (403 men and 527 women) respondents. Findings indicated that ACEs had a cumulative effect on adults’ illicit drug use. Each additional ACE increased drug use frequency by 0.087 units (p < 0.05). Biological sex (b = -0.446, p < 0.001), number of biological children (b = -0.155, p < 0.01), anxiety symptoms, (b = 0.071, p < 0.001), adolescent drug use (b = 0.166, p < 0.001), and residing with other substance-using individuals (b = 1.127, p < 0.001) were also significant correlates of illicit drug use in adulthood. Mediation analyses revealed that respondents’ anxiety symptoms and adolescent drug use mediated the total effect of ACEs on adults’ drug use frequency. Based on these results, it is argued that clinicians and others working with those who are at risk for or who are presently using illicit substances should consider how early life adversity influences drug use, both directly and indirectly via proximal risks.