Although wetting dynamics of liquids on solid surfaces has been studied for decades, via both experimental investigation and theoretical analyses, the physical mechanism still remains obscure. One of the major difficulties is that wetting dynamics is actually dominated by interfacial reactions at the molecular level. In this study, the dynamic contact angle and contact line deformation of a water droplet on a well-confined amorphous polytetrafluoroethylene (PTFE) surface was examined by molecular dynamics (MD) simulation. The force field parameters of PTFE structures were based on the OPLSAA force field in Gromacs 5.1.2. Our MD simulation yielded a satisfactory glass transition temperature of 118.8°C. A confined-layer method was used to construct a flat PTFE surface by smoothing out the intrusion or extrusion-induced roughness. Four cases for water droplets with different diameters were simulated. The static contact angle of water droplets was found to be ∼110.6° on PTFE. An exponential relationship was verified to describe the contact area development in the wetting process. By comparing our MD results with the hydrodynamics theory and molecular kinetics (MKT) theory, the viscous and molecular friction coefficients were determined to be on the order of 10−4kg/m · s. The MKT theory demonstrates excellent agreement with our MD results in the whole range of contact line velocity, while slight deviation exists in fitting hydrodynamics theory to high contact line velocity region. For the first time, a dimensionless number Nt was proposed to quantify the relative fluctuations of contact line velocity in this study.