Although emotional responses are theorized to be important in the development of empathy, findings regarding the prediction of early empathic behavior by infant behavioral and physiological responses are mixed. This study examined whether behavioral and physiological responses to mild emotional challenge (still face paradigm and car seat task) in 118 infants at age 6 months predicted empathic distress and empathic concern in response to an empathy-evoking task (i.e, experimenter’s distress simulation) at age 20 months. Correlation analyses, corrected for sex and baseline levels of physiological arousal, showed that stronger physiological and behavioral responses to emotional challenge at age 6 months were positively related to observed empathic distress, but not empathic concern, at age 20 months. Linear regression analyses indicated that physiological and behavioral responses to challenge at 6 months independently predicted empathic distress at 20 months, which suggests an important role for both physiological and behavioral emotional responses in empathy development. In addition, curvilinear regression analyses showed quadratic associations between behavioral responses at 6 months, and empathic distress and empathic concern at 20 months, which indicates that moderate levels of behavioral responsivity predict the highest levels of empathic distress and empathic concern.