Nowadays, although the exploration of proton conductive materials has ranged from traditional sulfonated polymers to novel crystalline solid materials such as MOFs, COFs, and HOFs, research on crystalline cluster-based organic framework materials is very limited. Here, a pair of homologues Cu(I)-based organic framework containing a Cu₁₂S₆ cluster, [Cu₁₂(MES)₆(H₂O)₃]_n (1) and {[Cu₁₂(MPS)₆(H₂O)₄]·6H₂O}_n (2) (H₂MES = 2-mercaptoethanesulfonate acid and H₂MPS = 2-mercaptoethanesulfonate acid), were hydrothermally synthesized under the same conditions and fully investigated for their proton conduction. Their structures were characterized by means of single-crystal X-ray diffraction, elemental analysis, thermogravimetric analyses, and PXRD measurements. The two MOFs show significant structural differences in the topological fashions. MOF 1 has a three-dimensional network and can be simplified into two topology types: a 10-connected gpu structure with a Schläfli symbol (3¹²·4²⁶·5⁷) and a 3,12-connected new topology with a point symbol {3·4²}₂{3¹⁰·4¹⁸·5¹⁹·6¹⁴·7⁴·9}. MOF 2 also has a three-dimensional framework and topology as a 6-connected pcu primitive cubic network with a Schläfli symbol {4¹²·6³}. The two MOFs show different proton conduction parameters, but both indicate temperature-dependent proton conductive features. Intriguingly, the two MOFs exhibit high water stability and their proton conductivities are 3.63 × 10⁻⁵ and 2.75 × 10⁻⁵ S cm⁻¹ under 333 K and 98% RH, respectively. The suggested mechanism for the synthesis for 1 and 2, and their proton conductivity performance comparison has been discussed in detail. In addition, Hirshfeld surface and fingerprint analysis on the two MOFs were computed to compare contacts between the molecules, which is essential for analyzing the relationships between their hydrogen bonds and proton conductivity properties.