Phosphogypsum (PG) is a by-product of the production of fertilizers from phosphate ores, and it contains some harmful substances to the environment. Thus, it is necessary to stabilize/solidify pollutants when using PG as a filling material. The purpose of this study is to investigate and verify the use of PG as a filling material for a road base through laboratory tests for a case study in Vietnam. In this study, PG incorporated with fly ash was stabilized with cement and lime. The specimens of these mixtures were then prepared and cured under wet and dry conditions. The mechanical properties of specimen were investigated through the unconfined compressive strength (UCS), California bearing ratio (CBR), and modulus of elasticity. The physical property of this stabilization was examined using scanning electron microscopy. A toxicity characteristic leaching procedure test was also conducted to assess environmental impact. The results showed that when PG was replaced partially by other materials such as cement, fly ash, lime, or sand, the maximum dry densities of specimens were increased, and their optimum moisture contents were decreased. The inclusion of 10% of FA and 10% of cement or 20% of FA, 5% of lime, and 5% of cement significantly enhanced the UCS of specimens using PG at the ages of 28 days. The compressive strength under the dry condition was higher than that under the wet condition. Additionally, all mixtures showed a higher modulus of elasticity and CBR value than the requirement of road base material. The utilization of original PG can be successfully used as raw material in stabilization for applying in the pavement layers of road construction. The obtained results in the present work showed that the physico-mechanical properties in terms of unconfined compressive strength, modulus of elasticity, CBR of PG specimens could satisfy the requirement for the subgrade, subbase, or base course of road construction even when the content of PG comes up to 90%.