The college years are marked by social changes and behavioral experimentation which may increase risk of suicidal ideation. We propose a novel pathway for the development of suicidal thoughts between two established suicide risk factors, loneliness and drug use, which have not been examined in a nonclinical sample. Data were collected from 207 undergraduate drug-using students at a large southeastern university. As hypothesized, suicidal ideation was positively correlated with both loneliness (r = .40) and drug use (r = .29). After controlling for several demographic variables, social desirability, and anxiety sensitivity, drug use was tested as a potential mediator in the loneliness–suicidal ideation link using a single-mediator model. Results indicated a significant indirect (mediated) effect of loneliness on suicidal ideation via drug use (ab = 0.09, 95% CI: 0.02–0.18), suggesting that loneliness may contribute to suicidal ideation through increased drug use among college students. Identification of and intervention with students reporting loneliness and drug use may be a promising suicide prevention strategy on college campuses.