Recently, researches have revealed that synaptic transistors based on two-dimensional materials (2DMs) have substantial advantages and potential for modeling neural synapses. However, the mechanism of artificial synaptic device with 2DMs as conducting channels remains to be further clarified. Here, high-quality wafer-scale MoSe2 nanosheets were achieved by ALD-CVD process, where further 23 × 23 × 4 synaptic arrays were fabricated in situ. Notably, the outstanding MoSe2 synaptic device exhibits an on/off ratio of 3.6 × 107 with hysteresis ratio of 6.8k and simulates crucial biological synaptic behaviors such as paired pulse facilitation and excitatory postsynaptic currents. The mechanism of Se vacancy induction and horizontal diffusion driven is revealed based on high-resolution transmission electron microscopy characterization with first-principles calculations, which suggests a possible mechanistic explanation for the resistive switching behavior of 2DMs transistors. Artificial synaptic devices with 2DMs based on the working mechanism of vacancy diffusion are capable of satisfying the needs of complex neural network applications.