“Open-framework chalcogenides” are an important class of materials that combine porosity with semiconductor behavior, and yet fundamental aspects of their conductivity remain unexplored. Here, we report a combined experimental-computational approach to the iconic subclass of materials TMA2MGe4Q10 (TMA = tetramethyl ammonium; M = Mn, Fe, Co, Ni, Zn; Q = S, Se). Direct current (DC) conductivity measurements and density functional theory (DFT) modeling reveal that metal ion and chalcogenide identities dominate key properties of the band structures, while impedance spectroscopy reveals purely electronic band-type transport in the Fe frameworks and redox-type mixed ion-electron conductivity in the others. Redox chemistry and computation suggest that the unique conductivity of Fe arises from its propensity toward Fe2+/Fe3+ mixed valency as a source of p-type doping and from its highly covalent bonds that ensure high carrier mobilities. Taken together, these results demonstrate open-framework chalcogenides as a well-defined platform for understanding porous semiconductors and for achieving highly tunable electronic performance.