In this study, a fully immersive Virtual Reality (VR) based driving simulator was developed to serve as a “proof-of-concept” that VR can be utilized to assess the level of fatigue (or drowsiness) truck drivers typically experience during real-life driving conditions. This study also involved examining the impact of varying driving conditions (i.e., weather conditions and driving time (day or night)) on drivers’ fatigue measure. To fulfill these goals, four drivers (two fatigued and two unfatigued) were allowed into the developed VR-based driving simulator to drive a VR-based truck at varying driving conditions. These conditions included clear day time, rainy day time, clear night time, rainy night time, foggy day time, rainy foggy day time, foggy night time, and rainy foggy night time conditions.