Little is known of Mr. Ghool before his first documented clashes with the Star-Spangled Kid and Stripesy in the early 1940s. A criminal mastermind possessing no superhuman ability, he relied instead on theatrical menace, poison, disguise, and a gang of henchmen, and concealed himself behind a ghastly, skull-like face that witnesses repeatedly likened to something out of a nightmare.

In the first documented case, Mr. Ghool sent a coffin and a gloating note to district attorney Morton B. Randall, promising that Randall would lie at rest within it by evening. The Pemberton family — including their seemingly indolent son, Sylvester, secretly the Star-Spangled Kid, and their chauffeur Pat Dugan, secretly Stripesy — were visiting Randall when Ghool and his ghoulish-faced henchmen burst in and overpowered the household. Randall was forced to drink a poison that left him in a deathlike pallor, and Sylvester was dragged off to be killed, giving him the opening to change into the Star-Spangled Kid while Dugan became Stripesy. In the ensuing brawl the Kid caught a bomb Ghool hurled and threw it from the window; Ghool seemingly took the blast but slipped away. The trail led to a cemetery, where Ghool had been running a grave-robbing operation and hoarding a fortune in an underground chamber, and where he had masqueraded as the cemetery's keeper. He revealed that Randall was not dead but held in suspended animation, the antidote his alone to give, and threatened to make the heroes "living corpses" as well. The pair freed themselves, scattered the henchmen, unmasked the keeper as Ghool himself, and forced him to revive Randall before sealing the gang in their own chamber — though Ghool escaped capture. (Star-Spangled Kid #4)

His next recorded campaign followed an escape from Kinstead Prison. Years earlier, Ghool had buried stolen loot on an empty lot, only to return from prison and find a skyscraper rising atop it. To recover the money he set out to halt the construction by terror, slugging a night watchman, poisoning workmen's food, sabotaging girders, and threatening the laborers until they quit the "jinxed" building en masse. The Star-Spangled Kid and Stripesy worked the case from the air in their Star-Rocket-Racer and undercover as laborers, repeatedly thwarting his attempts. Ghool, now armed with a nerve-gas gun that briefly paralyzed his targets, captured the pair, bound them in a construction elevator rigged with a cut cable and a bomb, and sent it aloft; but Stripesy shook off the gas, freed them both, and the Kid snatched out the bomb's fuse in time. Cornered atop the unfinished structure, Ghool confessed his motive and was beaten and delivered back to Kinstead Prison, with his captors observing that he was too slippery to stay behind bars for long (World's Finest #7).

The activities of Mr. Ghool after these encounters have not been recorded.