Single crystal of a thallium‐containing sulfate Tl2Pb(SO4)2 was prepared through hydrothermal crystallization starting from Tl2CO3, Pb(NO3)2 and H2SO4. The crystal structure was solved from single‐crystal X‐ray diffraction data: Tl2Pb(SO4)2 crystallizes in space group R[[EQUATION]]m with lattice parameters of a = 5.5955(2) Å, c = 22.1001(9) Å, and Z = 3, which is also corroborated by Rietveld refinement on X‐ray powder data. The crystal structure can be regarded as [Pb(SO4)2]2‐ sheets intercalated by double layers of Tl+ along the c‐axis. From a mineralogical perspective, Tl2Pb(SO4)2 belongs to the palmierite family and can further be classified within palmierite‐supergroup. Validation of the structure models was carried out utilizing various concepts including Bond Valence (BV), Charge Distribution (CD) and Madelung Part of Lattice Energy (MAPLE). Notably, a contrast in stereochemical activity of 6s2 lone electron pair (LEP) between Tl+ and Pb2+ is interpreted in terms of bonding behaviours as well as Wang‐Liebau Eccentricity (WLE) parameters. Moreover, an extensive investigation into the crystal chemistry of thallium‐containing sulfates was conducted for the first time, focusing on the coordination environment and bonding behaviour of Tl+ and corresponding WLE parameters. A comparative analysis of these structurally related compounds including Tl2Pb(SO4)2, Tl3H(SO4)2, TlBi(SO4)2, TlIn(SO4)2, TlRh(SO4)2, and TlAl(SO4)2 was delineated.