This study examined the association of perceived social support and community empowerment among urban middle-school students living in Matamoros, Mexico and the risk behaviors of fighting, alcohol and tobacco use, and sexual activity. Middle school students (n = 1,181) from 32 public and private Mexican schools were surveyed. Weighted multiple logistic regression analyses were conducted. Among girls, lack of parent/teacher interactions regarding school increased odds for fighting, alcohol and tobacco use. Among boys, lack of empowerment increased odds of alcohol and tobacco use and lack of parent/teacher interactions regarding school increased odds for sexual activity. Community empowerment and perceived social support are uniquely associated with risk behaviors for girls and boys. Additionally, perceived social support from individuals most immediate to the youth are associated with protection against risk for some behaviors, while perceived social support from individuals more removed from youth have mixed association with risk behaviors.