This study, through molecular dynamics simulations and the Tersoff potential function, explored how circular defects of the same size affect the biaxial tensile mechanical properties of single-layer graphene. The results showed that these defects significantly reduce the tensile strength and Young’s modulus of graphene. The impact of defects at the center position exceeds that of edge defects. The direction and distribution of defects determine their impact on model stability. Structures show greater stability when the direction of defects aligns with their distribution; conversely, structures are more prone to damage when the defect direction is perpendicular to the distribution. Different arrangements of defects have varied effects on the mechanical performance of graphene. Arrangements of defects parallel to the loading direction enhance the structure’s stability and relatively improve mechanical properties. This research provides important insights into understanding and improving the mechanical performance of graphene, especially in the fields of material design and engineering applications. Future studies will focus on how defects of different sizes and shapes affect the biaxial tensile performance of graphene and its behavior under complex loading conditions.