Many stress-related parameters have been associated with antisocial behavior, including low cortisol awakening responses (CAR), as well as low cortisol and alpha-amylase reactivity to stress. These parameters reflect different, yet interrelated components of the stress system, yet it remains to be determined whether they exert joint or independent effects. Therefore, this study examined them in concert, as this may offer a better explanation of the psychophysiological mechanism’s underlying antisocial behavior. Antisocial behavior was assessed through self-report by 197 general population boys and girls (Mage = 17.31, SD = 0.44). The CAR was assessed, as well as cortisol and alpha-amylase reactivity to a public speaking task. Neither stress-related parameter was independently related to antisocial behavior. The best explanation was provided by a CAR × Cortisol reactivity interaction, indicating that in youth with a low CAR, antisocial behavior was positively associated with cortisol reactivity. In youth with a high CAR, no association between antisocial behavior and cortisol reactivity was found. Between cortisol and alpha-amylase reactivity a trend toward an interaction appeared, indicating a negative association between cortisol reactivity and antisocial behavior in those with low alpha-amylase reactivity, and a positive association in those with high alpha-amylase reactivity. These findings indicate that in order to understand the mechanisms underlying antisocial behavior, the stress system should be studied comprehensively rather than focus on single parameters. Particularly cortisol parameters appear to be jointly related to antisocial behavior, the additional value of alpha-amylase reactivity to cortisol reactivity may however be limited.