Reactions of the main-group cation TlI with anions of 2,5-derivatives of TCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) have led to the isolation of a family of unprecedented semiconducting main-group-metal–organic frameworks, namely, [Tl(TCNQX2)], (X=H, Cl, Br, I). A comparison of single-crystal and powder X-ray diffraction data revealed the existence of a third polymorph of the previously reported material Tl(TCNQ)] and two distinct polymorphs of [Tl(TCNQCl2)], whereas only one phase was identified for [Tl(TCNQBr2)] and [Tl(TCNQI2)]. These new results are described in the context of the structures of other known binary metal–TCNQ frameworks that display a variety of coordination environments for the central cation, namely, four-, six-, and eight-coordinate, and different arrangements of the adjacent TCNQ radicals—parallel versus perpendicular—in the stacked columns. The halogen substituents affect the structures and the properties of these compounds, owing to both steric and electronic effects as evidenced by the semiconducting properties of crystals of [Tl(TCNQCl2)] phase I, [Tl(TCNQBr2)], and [Tl(TCNQI2)], which correlate well with the distances of adjacent TCNQ radicals in the columns. 1D infinite Hückel model simulations of the band structures of [Tl(TCNQCl2)] phase I, [Tl(TCNQBr2)], and [Tl(TCNQI2)] were conducted with and without consideration of the TlI cations, the results of which indicate that the charge mobility does not strictly occur in one dimension. The modulations of the band structures with various assumptions of the energy difference (Δ) between the TlI 6s orbital and the TCNQ LUMO orbital were calculated and are discussed in light of the observed properties.