The neurovisceral integration model posits that cognitive-behavioral inflexibility arises from biological inflexibility of feedback loops within the central autonomic network. The parasympathetic nervous system (PNS) is integral in this network. Activity of the PNS, which is normally tonically inhibited, can be indexed through respiratory sinus arrhythmia (RSA). When the PNS becomes disinhibited, indicating decreased flexibility within the network, RSA is reduced and cognitive-behavioral flexibility is impaired. Using this theoretical framework, cognitive-behavioral inflexibility is discussed from the Research Domain Criteria (RDoC) perspective. Restricted repetitive behaviors in autism spectrum disorder (ASD) are proposed as exemplars of cognitive-behavioral inflexibility, and behavioral and RSA literature in ASD are reviewed. RSA differences and their relation to inflexibility in ASD are discussed to support the model and to propose RSA as a biomarker for cognitive-behavioral inflexibility. Considerations for future research are discussed, in addition to implications the model might have on assessment and transdiagnostic treatment practices.