This paper describes the first demonstration of using a series of isoreticular nickel phthalocyanine- and nickel naphthalocyanine-based bimetallic conductive two-dimensional (2D) metal-organic frameworks (MOFs) as active materials in chemiresistive sensing of gases. Devices achieve exceptional sensitivity at sub-part-per-million (ppm) to part-per-billion (ppb) detection limits toward NH3 (0.31-0.33 ppm), H2S (19-32 ppb), and NO (1.0-1.1 ppb) at low driving voltages (0.01-1.0 V) within 1.5 min of exposure. The devices maintain their performance in the presence of humidity (5000 ppm of H2O). The isoreticular analogs enable modular control over selectivity and sensitivity in gas sensing through different combinations of linkers and metal nodes. Electron paramagnetic resonance spectroscopy and X-ray photoelectron spectroscopy studies suggest that the chemiresistive response of the MOFs involves charge transfer interactions triggered by the analytes adsorbed on MOFs.