This study explored drug use determinants in Ibadan's street youth by examining perceived stress and motives for drug use. A cross-sectional survey collected data from 125 youths sampled from various locations, including clubs, bars, brothels, and drug-selling and consumption spots. Most respondents (76.4%) were males, with age distribution as follows: 38.2% aged 14-25 years, 36.6% aged 26-35 years, 22.0% aged 36-45 years, and 3.3% aged 46 years and above. Analysis employed t-tests, multiple regression, and ANOVA at a 0.05 significance level. Results showed a significant positive link between fun and getting high motives (r = .22, p < 0.05) and drug dependency. Perceived stress, life event stressors, peer pressure, and reputation motives, as well as fun and high motives, exhibited significant positive relationships with drug dependency (p < 0.01). Perceived stress and drug use for fun and being high were significant predictors of drug dependency (R2 = .55, F = 28.85, p < .01). Age also significantly predicted drug dependency (β = -.48, p < .05). Nonetheless, there was no joint influence of age, gender, marital status, and educational status on drug use (p > .05). In summary, motives for drug use and life stressors were identified as predictors of drug use among Ibadan's street youth. The study recommends early implementation of comprehensive, multi-component prevention programs with adequate duration, scope, and intensity to address substance abuse in this population.