Due to the complex aerodynamic interaction, the safe separation of two stages is one of the challenges for the successful launch of a two-stage-to-orbit (TSTO) vehicle. The unsteady hypersonic flow past the parallel-staged TSTO model during stage separation at Ma = 6.7 and Re = 8.86 × 105 m−1 is numerically studied using laminar flow simulation. The TSTO model consisted of a waverider and a spaceplane as booster and orbiter, respectively. The effect of the center of gravity (CoG) of the orbiter on the unsteady aerodynamic interference during stage separation of TSTO is analyzed in detail with 0.65 ≤ lCoG/lo ≤ 0.80. In addition, the aerodynamic characteristics, dynamic behaviors, and unsteady wall pressure variation are compared in different cases. The results show that the CoG regime is limited to 5% of the orbiter length for absolutely safe separation, i.e., 0.70 < lCoG/lo < 0.75. As for the unsuccessful separation, the orbiter tends to fly nose-down if lCoG/lo ≤ 0.70 while tending to pitch or somersault when lCoG/lo = 0.80. Furthermore, the pitching moment of the orbiter, which is influenced by the interstage shock wave–boundary layer interaction and shock–shock interaction, dominates the separation safety, and the specific flow mechanisms concerning the separation behavior associated with aerodynamic interference in different cases are analyzed in detail.