Abstract Objectives Pre-historic decline in human craniofacial masculinity has been proposed as evidence of selection for elevated sociability and a process of ‘human self-domestication’ thought to have promoted complex capacities including language, culture, and cumulative technological development. This follows experimental observation of similar changes in non-human animals under selection for reduced aggression. Two distinct domestication hypotheses posit developmental explanations, involving hypoplasia of embryonic neural crest cells (NCCs), and declining androgen influence, respectively. Here, I assess the operation and potential interactions between these two mechanisms and consider their role in enhanced human adaptation to a cooperative sociocultural niche. Methods I provide a review and synthesis of related literature with a focus on physiological mechanisms effecting domesticated reductions in masculinity and sexual dimorphism. Further, I examine pre-historic modes of socio-sexual selection likely to drive human self-domestication via reduced aggression and masculinity. Results I find pluripotent NCCs provide progenitors for a wide range of vertebrate masculine features, acting as regular targets for sexually driven evolutionary change; suggesting domesticated hypoplasia of NCC-derived tissues would be sufficient to explain declines in masculine traits and features. However, lineage specific androgen receptor variability likely moderates these NCC-based effects. Conclusions These findings extend theorised mechanisms driving noted physiological, morphological, and behavioural changes thought to indicate enhanced sociability and human and self-domestication. Multiple current explanations for human sociability are consistent with physiological domestication under socio-sexual selection favouring dampened masculine physiology and behaviour as adaptations to an enhanced sociocultural niche. The analysis highlights multiple avenues for further investigation.