Traffic interruption by lane closures in construction work zones (CWZ) is unavoidable when road maintenance activities are undertaken. This study evaluated the fuel consumption and greenhouse gas (GHG) emissions generated by on-road vehicles under various CWZ situations for highway maintenance and rehabilitation. The scenario factorials were developed considering traffic volumes, vehicle types, drive cycles, highway categories, and work zone traffic operation plans. Fuel consumption and GHG emissions were selected as the environmental impact indicators and were estimated using the motor vehicle emission simulator (MOVES). For the freeway scenarios, fuel consumption, and GHG emissions increased by 85 percent and 86 percent, respectively, under heavily congested CWZ compared to free flow condition without CWZ. For the multilane (4-or 6-lane) road scenarios, fuel consumption, and GHG emission increased by 83 percent and 84 percent, respectively, under heavily congested CWZ, compared to uncongested traffic condition without CWZ. Mitigating CWZ traffic congestion from heavy (average speed 5 mph) to medium congestion (average speeds 25 mph for a freeway and 15 mph for a multilane road) in the CWZ would reduce fuel consumption and GHG emissions by 40 percent on a freeway and 32 percent on a multilane road. The study results are useful to analyze pavement life cycles with alternative maintenance treatments, lane closure strategies, and construction/traffic management plans.