The isostructural phase transitions such as in compressed molybdenum disulfide (MoS₂) are ubiquitous in nature, but surprisingly, how and why the vertical compression driven lateral interlayer sliding are still open questions of interest. Here, we address the tribological determination of the pressure-driven interlayer sliding for the structural and electric tuning in compressed MoS₂ bilayer by using ab initio calculations. The density functional calculations demonstrate the pressure-driven evolution of interlayer potential energy landscape, providing the preferred sliding pathway for initiating mutual sliding of crystal faces between MoS₂ bilayers. Interestingly, even though the 2H _a stacking becomes more stable than the 2H _c stacking at a load of about 9.2 GPa, a spontaneous slippage would take place only around 30.1 GPa, when the sliding barrier of saddle stacking vanishes as a consequence of the load-driven modification of the potential energy surface. The structural transition from 2H _c -MoS₂ to 2H _a -MoS₂ is thus triggered, which allows for the semiconductor–metal transition of the bilayer under pressure. These results agree with recent experimental and dynamics observations of the transition occurring almost completely at 28–30 GPa in bulk crystals. By elucidating these criteria, we suggest that the study may be thus extended to understand the macroscopic properties of the bulk layered crystals such as the possible occurrence of phase transitions taking place at solid interfaces from the atomistic sliding mechanisms at the microscopic scale.