Driving is a complex task that consists of several physical (motor-related) and physiological (biological changes within the body) processes occurring simultaneously. The complexity of the task depends on several factors, but this research focuses on work zone configurations and their effect on driver performance and gaze behavior. The increase in work zone fatalities in the United States between 2015 and 2018 coupled with the limited literature of driver behavior in these complex environments requires a more comprehensive study. Given the nature of these crashes, typically lane departures, gaze behavior provided an additional physiological dimension to the present research. A framework that comprises of the interactions between driver characteristics, mental workload, and situation awareness, with longitudinal control, lateral control, and gaze behavior is proposed. Crash analysis and a simulator study with 90 participants were carried out to investigate the performance and gaze-based changes with respect to various work zone configurations. Distracted driving was also studied by including a secondary task. The results showed a significant interaction between the longitudinal control and the standard deviation of horizontal gaze position in predicting lateral control. Also, significant differences in lateral control and horizontal gaze variations were observed between genders. Female drivers showed lower lateral position deviations and lower horizontal gaze variability. This was a key finding given the inherently higher number of work zone crashes involving male drivers. Placing work zone barriers further away, by up to one meter from pavement edges, could significantly decrease mental workload and improve safety in work zones.