Localized rheological weakening is required to initiate and sustain intracontinental orogenesis, but the reasons for weakening remain debated. The intracontinental Alice Springs orogen dominates the lithospheric architecture of central Australia and involved prolonged (450–300 Ma) but episodic mountain building. The mid-crustal core of the orogen is exposed at its eastern margin, where field relationships and microstructures demonstrate that deformation was accommodated in biotite-rich shear zones. Rheological weakening was caused by localized melt-present deformation coupled with melt-induced reaction softening. This interpretation is supported by the coeval and episodic nature of melt-present deformation, igneous activity, and sediment shed from the developing orogen. This study identifies localized melt availability as an important ingredient enabling intracontinental orogenesis.