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Objective: A growing body of literature documents sexual problems following maltreatment and traumatic experience, but the mechanisms of these effects are poorly understood. The autonomic nervous system coordinates typical and threat-reactive functions throughout the body, including those of reproductive organs. We examined whether relations between adult sexual function problems and childhood maltreatment history could be mediated by an autonomic nervous system retuning with a bias toward maintaining a physiological state that supports defensive strategies. Method: Self-reported data on childhood physical abuse, emotional abuse, sexual abuse, physical neglect, emotional neglect, autonomic reactivity, and adult sexual function were collected from an online sample of U.S. residents 18 years and older (189 males and 333 females). Mediation was tested using indirect effects in structural equation modeling with age as a covariate. Results: Mediation via subjective reports of autonomic reactivity was supported in males and females (standardized indirect effect in males = −.35 [95% CI: −.53, −.20]; females = −.09 [95% CI: −.17, −.03]). The direct effect of childhood maltreatment was not significant with the addition of the mediator, supporting full mediation. Follow-up analyses indicated that the mediation effect remained even after those with sexual abuse were excluded from the male model (standardized indirect effect = −.30 [95% CI: −.61, −.10]) but not the female model. Conclusions: A chronic autonomic state that supports biobehavioral defense following abuse and trauma may contribute to adult sexual function problems, particularly in males and may point toward new treatment opportunities that target the autonomic nervous system.