Electrically conductive two-dimensional (2D) conjugated metal–organic frameworks (c-MOFs) are emerging electronic materials with tunable topologies and metal nodes. However, the uniform reactivity of conventional high-symmetry ligands typically leads to homogeneous linking, limiting the programmable construction of diverse topologies and metal nodes from a single-type ligand. Here we report an anisotropic reticular chemistry strategy using the 1,2,5,6,9,10,12,13-octahydroxydibenzo-[fg,op]naphthacene ligand with diverse catechol reactivities to construct seven distinct c-MOF crystals. Site-selective coordination of 1,2,5,6,9,10,12,13-octahydroxydibenzo-[fg,op]naphthacene yields three topologically distinct copper-based c-MOFs, including 2D square-arranged (Cu-2D-sql), 2D honeycomb-arranged (Cu-2D-hcb) and one-dimensional linear (Cu-1D) structures. Cu-1D could further react with metal ions to produce four bimetallic CuM-2D-sql (M = Ni, Co, Zn or Mn) with defined bimetal node arrangements. Theoretical modelling and single-crystal electrical measurements reveal that this structural programming effectively modulates the charge transport behaviour. The anisotropic reticular chemistry strategy thus provides a route towards atomic-level control over the structures and electronic properties of conductive frameworks. (Figure presented.)