Non-medical prescription opioid (NMPO) use and depression frequently co-occur and are mutually reinforcing in adults, yet NMPO use and depression in younger populations has been under-studied. We examined the prevalence and correlates of depressive symptomology among NMPO-using young adults. The Rhode Island Young Adult Prescription Drug Study (RAPiDS) recruited young adults in Rhode Island who reported past 30-day NMPO use. We administered the Center for Epidemiologic Studies Short Depression Scale (CES-D 10), and used modified Poisson regression to identify the independent correlates of depressive symptomology (CES-D 10 score ≥10). Over half (59.8%, n = 119) screened positive for depressive symptomology. In modified Poisson regression analysis, diagnostic history of depressive disorder and childhood verbal abuse were associated with depressive symptomology. Participants with depressive symptomology were more likely to report using prescription opioids non-medically to feel less depressed or anxious, to avoid withdrawal symptoms, and as a substitute when other drugs are not available. Among young adult NMPO users, depressive symptomology is prevalent and associated with distinct motivations for engaging in NMPO use and represents a potential subgroup for intervention. Improving guidelines with tools such as screening for depressive symptomology among young adult NMPO users may help prevent NMPO-related harms.