The presence of work zones due to pavement repair and rehabilitation is very common in highway facilities. Lane closures associated with work zones result in capacity reduction, which, in turn, often leads to increased congestion at such locations. This paper documents findings from a study that investigated the performance of freeway facilities in the presence of work zones under various Temporary Traffic Control (TTC) and lane closure scenarios while taking under consideration traffic composition and driving behaviors. The study site was an approximately 10-mile freeway segment of Interstate 65 (I-65) located in Birmingham, AL. The testbed was coded in PTV VISSIM, a microscopic simulation analysis platform, for: 1) baseline conditions (i.e., no work zone presence) and 2) work zone conditions with single lane closure (i.e., 3-to-2 lane closure). Work zone scenarios were coded for two TTC strategies, namely, early merge and late merge control and for three different positions of the lane closure (i.e., left, right, and center lane closures). The length of the work zones varied from 1000 to 2000, and 3000 ft. Sensitivity analysis was performed to document the operational impacts of varying heavy vehicle percentages, changes in drivers’ aggressiveness, and projected traffic demand changes. The impacts were quantified using linked-based measures of effectiveness (MOEs) such as travel time, and travel time index. The study results show that there is no significant change in travel time index due to the variation of work zone length across the study corridor. Under similar traffic control and demand conditions, a center lane closure consistently results in significantly higher travel time index than a left or right lane closure and should be avoided. Consideration of operational impacts of changes in truck percentage indicates that the corridor can absorb an increase in truck percentage from 10% to 15%, while performance rapidly deteriorates when a higher percentage of trucks is present in the traffic stream. The study findings can be used to guide transportation agencies in their future efforts to develop strategic lane closure plans that minimize congestion.