There is a need to understand how the joint development of externalizing and internalizing behaviors is related to substance use, particularly among historically understudied and often disadvantaged populations. Latent class models were used to estimate patterns of externalizing behaviors and internalizing behaviors in the form of depressive and anxious symptoms from age 6 to 14 among 390 Black and Hispanic youth. Then, growth curve models of substance use between the ages of 15 and 19 were estimated as a function of joint latent class membership. Only elevated levels of externalizing behaviors were associated with higher levels of substance use through age 18. Internalizing behaviors appeared to serve as a protective factor among those with moderate displays of externalizing behavior only. Additionally, growth in substance use from ages 15 to 19 was slower among those who displayed the highest level of externalizing behaviors, and internalizing behaviors appeared to moderate growth (and serve as protective factor) among those who displayed moderate levels of externalizing behaviors. The findings underscore the importance of pattern profiles based on observations of the joint development of problem behaviors to assess risk for substance use, particularly in understudied populations where risk/protective factors may operate in a unique manner.