Utilization of fly ash in concrete reduces the use of virgin materials and offers benefits of reduced landfill materials and CO2 emissions avoidance—fly ash therefore contributes to industrial sustainability. This paper presents a method to optimize the cement and fly ash contents in concrete on the basis of the hardened concrete properties testing and environmental effects. Such fly ash concrete would develop an adequate 1-day and 28-day compressive strength and would be as durable as the ordinary portland cement concrete. Nine concrete mixtures with fly ash contents ranging from 15–60% and cementitious material contents from 338–391 kg/m3 (570−705 lbs/cu yd) were investigated. Environmental life cycle assessments (LCA) were completed by using a model developed for Denver, Colorado. The optimized fly ash concrete was selected to yield a similar 28-day compressive strength and durability to that of Colorado Department of Transportation (CDOT) Class D structural concrete. The durability aspects investigated included the resistance to rapid chloride-ion penetration and the resistance to the rapid cycles of freezing and thawing. The results show that the mixtures with cementitious material content lower than 365 kg/m3 (615 lbs/cu yd) and fly ash content higher than 40% meet the CDOT Class D structural concrete strength and durability requirements. On the basis of the structural performances of the concrete mixtures and environmental effects, the optimized cementitious material content and the maximum possible cement replacement percentage with the fly ash was selected to be 338 kg/m3 (570 lbs/cu yd) and 50%, respectively. The optimized concrete mixture exhibited excellent characteristics in compressive strength (32.0 MPa, 4,635 psi at 28 days), resistance to chloride-ion penetration (moderate at 28 days of age) and freeze-thaw (96, average durability factor after 300 cycles). The mixture with optimum fly ash and cementitious content had the minimum embodied energy and greenhouse gas (GHG) emission among the nine mixtures. The embodied energy and GHG emission of the optimized concrete mixture (per cubic meter) were 2,643 MJ and 361 kgCO2E, respectively, which are 32.8 and 35.2% less than the mixture with the most embodied energy and GHG emission.