This paper describes two key objectives. The first objective is to develop a method of predicting and quantifying the amount of water that can enter into a pavement system by vapor transport. The second objective is to identify the extent to which fatigue crack growth in pavement would result from such moisture accumulation. To fulfill these two objectives, a diffusion model was first established to illustrate the wetting process of the surface asphalt layer caused by the vapor migration from subgrade soil into the upper layer. Second, to quantify the degree of moisture damage induced by water vapor diffusion, fine aggregate mixture specimens were fabricated and conditioned at different levels of relative humidity (RH) in closed vacuum desiccators that allow little temperature fluctuation. Moreover, the moisture-conditioned specimens were tested with a newly developed repeated direct tension (RDT) test method to evaluate the fatigue crack growth. The RDT test greatly reduced the stress state complexity within the specimens by evenly distributing stress over the cross-sectional area of the cylindrical specimen. Compared with the previous torsional test, the newly proposed test protocol was more efficient in characterizing the moisture susceptibility of the asphalt mixture. A major finding of this study is that higher RH levels in an asphalt surface layer will induce significantly higher crack growth rates.