Two‐dimensional layered transition metal dichalcogenides (TMDCs) are promising memristive materials for neuromorphic computing systems. Despite extensive experimental work, the underlying switching mechanisms are still not understood, impeding progress in material and device functionality. This study reveals the dominant role of defect dynamics in the switching process of 2D TMDC materials. The switching process is governed by the formation and annihilation dynamics of a local vacancy depletion zone. It explains the distinct features of the device characteristics observed experimentally, including fundamentally different device behavior previously thought to originate from multiple mechanisms. Key influence factors are identified and discussed with a fully coupled and dynamic charge transport model for electrons, holes, and ionic point defects, including image‐charge‐induced Schottky barrier lowering (SBL). Thermal effects and local Joule heating are considered by coupling the transient heat transfer equation to the electronic properties. The model is validated with hysteresis and pulse measurements for various lateral 2D MoS2‐based devices, strongly corroborating the relevance of vacancy dynamics in TMDC devices and offering a new perspective on the switching mechanisms. The insights gained from this study can be used to extend the functional behavior of 2D TMDC memristive devices in future neuromorphic computing applications.