HYDRA is an authoritarian terrorist-criminal-paramilitary organization bent on world domination. It was founded in ancient times, formerly as a cult centered around the fanatical worship of Hive, a powerful Inhuman that was exiled to the planet Maveth by ancient Inhumans. Ever since his banishment, the cult had been determined to bring him back to Earth to commence a planetary takeover.

Over the centuries, the cult evolved, taking many forms, with its most recent incarnation coming into existence shortly after the rise of Nazism in Germany under the leadership of Johann Schmidt as the scientific branch of the Nazi Schutzstaffel. During this time, the cult took on the name HYDRA, which soon became the organization's most colloquial label.

During World War II, Schmidt separated HYDRA from Nazi Germany to start his own conquest of the world, and it was during or before this time when HYDRA seemingly abandoned the cult's original beliefs. Converting from occultism, to draconian anti-freedom principles, HYDRA became an organization with a hell-bent nature that is dedicated to this newfound political doctrine.

After its defeat at the hands of Captain America in 1945 and the subsequent disappearance of Johann Schmidt, HYDRA was secretly rebuilt inside S.H.I.E.L.D. by Schmidt's top scientist Arnim Zola, who was recruited into the agency during Operation Paperclip. Though Zola's body died in the early 1970s, HYDRA was already well established, and Zola's mind continued to live in a computer.

In the following decades, HYDRA orchestrated crises and planted roots worldwide; establishing a clandestine network of operatives engaged in political engineering and scientific research. HYDRA's endgame was the overthrow of world governments to establish a fascist, totalitarian global state; thus preemptively eliminating potential threats to their new world order.

By the end the 20th century, operatives of HYDRA had managed to spread outside of S.H.I.E.L.D., infiltrating many important organizations, including the United States Government and the World Security Council, eventually establishing many secret bases around the world. One of HYDRA's top agents in S.H.I.E.L.D., John Garrett, secretly led the Centipede Project with the goal to recreate the Super Soldier.

In 2014, HYDRA's plans for world domination almost succeeded through their agent Alexander Pierce and S.H.I.E.L.D.'s Project Insight. However, their plan to eliminate 20 million people who posed a threat to HYDRA failed because of the efforts of HYDRA's oldest enemy, Captain America, who publicly exposed their infiltration of S.H.I.E.L.D. and destroyed their main tool of destruction, three of S.H.I.E.L.D.'s Helicarriers, with Alexander Pierce being killed by S.H.I.E.L.D.'s former director Nick Fury in the process. However, HYDRA's leader Wolfgang von Strucker already had new plans for global domination, plans which included twins declared "miracles" and the Scepter.

With its existence publicly known, HYDRA started a war against the remnants of S.H.I.E.L.D., taking over many S.H.I.E.L.D. bases. For many months, HYDRA's forces led by John Garrett fought a vicious fight against the small team of loyal S.H.I.E.L.D. agents led by Phil Coulson. Despite its attempt to infiltrate the U.S. Armed Forces through Ian Quinn and the Deathlok Soldiers, Garrett's group was ultimately defeated through the combined efforts of S.H.I.E.L.D.'s former director Nick Fury, Coulson's team, and the U.S. Marines.

However, even that defeat was only a temporary setback for HYDRA. S.H.I.E.L.D. was destroyed and publicly declared a terrorist organization, and many HYDRA agents continued with their work, including the high ranking member Daniel Whitehall who used the fall of S.H.I.E.L.D. to start the campaign to recover the mysterious Obelisk.

However, the campaign ended disastrously for HYDRA. Whitehall was killed before he could fully exploit the Obelisk, his second in command Sunil Bakshi was captured, and many other heads of HYDRA were killed by HYDRA itself when S.H.I.E.L.D. fooled them into thinking that there was a power struggle within HYDRA's ranks.

Two of the remaining heads of HYDRA, Baron von Strucker and Doctor List, continued with their experiments on powered individuals. However, even their experiments came to an end when the Avengers attacked Strucker's fortress in Sokovia, killing List and capturing Baron von Strucker, who was later killed by the robot Ultron. Strucker's demise marked the end of HYDRA's militaristic and scientific faction, allowing for its more ancient roots to take control.

Two of the few remaining HYDRA leaders, Grant Ward and Gideon Malick, joined forces to rebuild HYDRA, destroy S.H.I.E.L.D., and bring Hive back to the Earth. Despite Ward's death on Maveth by the hands of Coulson, Malick's plan succeeded because Hive took possession of Ward's body and returned to the Earth in his reanimated corpse.

Hive slowly began taking control of some Inhumans, and at the same time took over the leadership of Malick's cell, which ended with Malick's death caused by Daisy Johnson. Hive eventually left HYDRA to seemingly perish in the military campaign led by Brigadier General Glenn Talbot.

Loyal to its oath, HYDRA survived even that defeat. A single cell led by the US Air Force officer General Hale continued its hunt for S.H.I.E.L.D. agents, and at the same time worked to save humanity from a threat from space.

Despite making a deal with the alien Confederacy, Hale hoped to transform her daughter to the strongest person on Earth in order to force them to alter the deal. However, S.H.I.E.L.D., whose core members had seen what appeared to be the catastrophic consequences of this project, intervened in her plans and even the prospect of ensuring the safety of humanity could not unite the two organizations as Hale had hoped. Hale was eventually killed by an enhanced and insane Talbot, leaving HYDRA's fate uncertain.