Hyper-systemizers are individuals displaying an unusually strong bias toward systemizing, i.e. toward explaining events and solving problems by appeal to mechanisms that do not involve intentions or agency. Hyper-systemizing in combination with deficit mentalizing capability typically presents clinically as an autism spectrum disorder; however, the development of hyper-systemizing in combination with normal-range mentalizing capability is not well characterized. Based on a review and synthesis of clinical, observational, experimental, and neurofunctional studies, it is hypothesized that repeated episodes of insightful problem solving by systemizing result in attentional and motivational sensitization toward further systemizing via progressive and chronic deactivation of the default network. This hypothesis is distinguished from alternatives, and its correlational and causal implications are discussed. Predictions of the default-deactivation model accessible to survey-based instruments, standard cognitive measures and neurofunctional methods are outlined, and evidence pertaining to them considered.