Literature suggests that reduced electrodermal reactivity (EDR) is related to externalizing problems. However, the genetic and environmental etiology of this association is unknown. Using a standard habituation paradigm, we measured responses to 15 loud tones in four cohorts of adolescent twins (N = 2,129). We quantified EDR as the average size of elicited responses (amplitude) and by counting the number of skin conductance responses (frequency). Externalizing liability was indexed through a general factor underlying substance-related problems and antisocial behavior. Response frequency, but not mean amplitude, was inversely associated with externalizing liability in each twin cohort. Biometric modeling revealed that most of the overlap between response frequency and externalizing liability was due to genetic influences common to both phenotypes. It is argued that neurological mechanisms involved in habituation may shed light on the etiology of psychopathology.