We investigated the structural stability of colloidal PbS nanocrystals (NCs) self-assembled into superlattice (SL) allotropes of either face-centered cubic (fcc) or body-centered cubic (bcc) symmetry. Small-angle X-ray scattering analysis showed that the NC packing density is higher in the bcc than in the fcc SL; this is a manifestation of the cuboctahedral shape of the NC building block. Using the high-pressure rock-salt/orthorhombic phase transition as a stability indicator, we discovered that the transition pressure for NCs in a bcc SL occurs at 8.5 GPa, which is 1.5 GPa higher than the transition pressure (7.0 GPa) observed for a fcc SL. The higher structural stability in the bcc SL is attributed primarily to the effective absorption of loading force in specific SL symmetry and to a lesser extent to the surface energy of the NCs. The experimental results provide new insights into the fundamental relationship between the symmetry of the self-assembled SL and the structural stability of the constituent NCs.