The thickness-dependent performances of metal-two-dimensional (2D) semiconductor junctions in electronics/optoelectronics have attracted increasing attention but, currently, little knowledge about the micro-mechanism of this thickness (or layer-number) dependence is available. Here, by first-principles calculations based on density functional theory, we show that the Fermi-level pinning (FLP) factor of a metal-2D multilayered semiconductor junction (MmSJ) has a sensitive dependence on the layer-number of the MmSJ for few-layer 2D semiconductors, in a proposed extension of FLP theory. Taking a MmSJ with MoS as a typical example, we find that strong pinning arises right at the metal-1st-layer semiconductor interface, while depinning occurs between the MoS layers. The depinning effect mainly contributes to the variation of the FLP factor as a function of the layer-number of the semiconductor, making p-type Schottky barrier contact more favorable in MmSJs than in metal-2D monolayer semiconductor junctions, especially for large work-function metals. Moreover, our results shed light on recent controversial experimental observations relating to MmSJs and metal-2D monolayer semiconductor junctions.