This study identifies mental health and situational predictors of arrest history among homeless youth in four U.S. cities. Using convenience sampling, we recruited 188 homeless youths from shelters, drop-in centers, and street outreach using similar methods. The youths, aged 18–24, came from Los Angeles, California (n = 50), Denver, Colorado (n = 50), New Orleans, Louisiana (n = 50), and St. Louis, Missouri (n = 38). General strain theory provided a framework for identifying factors related to arrest history, including length of time homeless, level of transience, victimization, post-traumatic stress disorder (PTSD), substance dependence, and the use of survival strategies. We tested the general strain model using observed-variable path analysis. Collectively, youths’ length of time homeless, drug dependence, and use of survival strategies explained 17% of the variance in arrest history. We found a significant overall mediation effect from transience to arrest history through greater victimization, post-traumatic stress disorder, drug dependence, and survival strategies. This study offers one of the first applications of general strain theory to identify both mental health and situational strains—and responses to strains—among homeless youth. Findings have important implications for research and preventive interventions to address delinquency among this population.