© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5,15-Dioxaporphyrin was synthesized for the first time by a nucleophilic aromatic substitution reaction of a nickel bis(α,α′-dibromodipyrrin) complex with benzaldoxime, followed by an intramolecular annulation of the α-hydroxy-substituted intermediate. This unprecedented molecule is a 20π-electron antiaromatic system, in terms of Hückel's rule of aromaticity, because lone pair electrons of oxygen atoms are incorporated into the 18π-electron conjugated system of the porphyrin. A theoretical analysis based on the gauge-including magnetically induced current method confirmed its antiaromaticity and a dominant inner ring pathway for the ring current. The unique reactivity of 5,15-dioxaporphyrin forming a β,β-linked dimer upon oxidation was also revealed.