| Character | Role |
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| Malebolgia | The first main antagonist, former master of the eighth circle of hell.Angel williams Angel williamsRev angel kyodo williams quotesRadical dharma pdfAngel kyotoAngel kyodo williams meditationDecapitated by Spawn. Exists as a ghost possessing the Freak's necroplasmic body. |
| Jason Wynn / Disruptor | Former CIA director and Al Simmons' superior who gave the order to kill Simmons. Was one of the most powerful men on the planet, later returning as the supervillain Disruptor.As Father said while he was here today, William lived a saintly life and lived a life with no sins. |
| Violator (Clown) | A major villain in the series, appearing as a Constant tormentor and the arch-nemesis of Spawn, pushing him to use his powers for the benefit of Hell. One of the five Phlebiac Brothers, demons from the eighth circle of Hell.
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| The Redeemer (originally known as Anti-Spawn) | Holy opposite to the Hellspawn, created by the Star Chamber. |
| Mammon | A Forgotten One. One of the major Lords of Hell and the second primary antagonist of the series.
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| Katie Fitzgerald (Satan) | Overarching antagonist; revealed in issue that she was actually Satan; killed
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