Background Although resting heart rate (RHR) and empathy are independently and negatively associated with violent behavior, relatively little is known about the interplay between these psychophysiological and temperament‐related risk factors. Methods Using a sample of 160 low‐income, racially diverse men followed prospectively from infancy through early adulthood, this study examined whether RHR and empathy during early adolescence independently and interactively predict violent behavior and related correlates in late adolescence and early adulthood. Results Controlling for child ethnicity, family income, and child antisocial behavior at age 12, empathy inversely predicted moral disengagement and juvenile petitions for violent crimes, while RHR was unrelated to all measures of violent behavior. Interactive effects were also evident such that among men with lower but not higher levels of RHR, lower empathy predicted increased violent behavior, as indexed by juvenile arrests for violent offenses, peer‐reported violent behavior at age 17, self‐reported moral disengagement at age 17, and self‐reported violent behavior at age 20. Conclusions Implications for prevention and intervention are considered. Specifically, targeting empathic skills among individuals at risk for violent behavior because of specific psychophysiological profiles may lead to more impactful interventions.