Following Loki's defeat, Red Skull assumed command of Hydra. His core motivation arose from the conviction that evil could not permanently triumph within the existing world order. This belief drove his ultimate scheme: to annihilate the current world and recreate it entirely under his dominion, where evil reigned supreme.

He orchestrated the prison break of the Celebrity Five, utilizing the Dimension Sphere to steal their complete set of biocodes. This theft granted him the unrestricted, indefinite power to D-Smash all DISK types. He distributed these biocodes among his subordinates. Next, he enlisted Mystique to procure DISKs containing Baron Zemo, Abomination, Tiger Shark, Graviton, and M.O.D.O.K. After betraying Mystique, he employed the Dimension Sphere to augment their powers, forging the enhanced Masters of Evil as his primary enforcers.

His endgame centered on abducting scientist Bridget Chan for her expertise on the planet's energy pathways, the Gaia Lines. He deployed the Masters of Evil to five global bases housing Gaia Anchors, commanding them to use the Dimension Sphere to corrupt these lines simultaneously. This synchronized corruption aimed to shatter the planet's stability at midnight, enabling its destruction and rebirth under his rule. He equipped the Masters with biocodes to D-Smash villainous minions during the operation.

When the Avengers thwarted the Gaia Anchor corruption, he intervened personally. Threatening Hikaru Akatsuki's brother Akira, he coerced Hikaru into absorbing a shard of the Dimension Sphere into his body. This act transformed Hikaru into his unwilling servant. Red Skull exploited this control to lure the Avengers into a confrontation, forcing Thor to battle his own allies under threat of Hikaru's death by the Sphere's energy.

Hawkeye, disguised as Crossbones after defeating and D-Securing the real henchman, infiltrated his inner circle and shot him during this clash. Despite Hawkeye's attempt to force Hikaru's liberation, the Dimension Sphere's energy was only expelled when Thor absorbed its blast. This allowed Hikaru to burn out the corruption, aided by his Biocode's self-repair system.

Undeterred, Red Skull activated Hydra's ultimate weapon: a giant robot powered by the Dimension Sphere, embodying the culmination of Hydra's technological knowledge. He piloted it against the combined forces of the Avengers, Hawkeye, Power Man, Iron Fist, Black Panther, and Falcon. Thor delivered the decisive blow, destroying the robot's cockpit and incapacitating him. Akira Akatsuki subsequently D-Secured him, ending his reign.