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The war between Big Boss and Zero was a conflict between Big Boss and his vision Outer Heaven, and Zero and his organization, the Patriots. The two could not agree on what The Boss's will truly was, and thus became bitter enemies.
In 1970, Zero founded the Patriots, whose aim was to carry on The Boss's will. However, over time, Zero became power hungry. He used Big Boss's fame as a way to gain influence. Big Boss grew to be resentful of Zero's twisted ways, and disliked being used for the latter's goals. Fearing Big Boss would leave the Patriots, Zero decided that he needed insurance against his former friend.
Two years later, in 1972, Zero and Dr. Clark extracted Big Boss's DNA.[note 1] After dozens of faliures, EVA was used as a surrogate mother to create two clones, who were later given the codenames Solid Snake and Liquid Snake. A third clone, who would be called Solidus Snake, was created later.
When Big Boss found out about the project, he left to form his own vision with Kazuhira Miller. The result was the creation of the PMC, Militaires Sans Frontières. Around this time, Zero, now having his organization go by the name Cipher, went into hiding and began plotting against Big Boss and MSF.
In 1974, Zero had his agent Paz Ortega Andrade stage the Peace Walker Incident to create a situation in which they could use Big Boss's own creation, Metal Gear ZEKE, against him and MSF. This was done in order to blackmail him into rejoining Cipher, with the ultimatum being the destruction of MSF's reputation. While the plan failed, Zero was unconcerned, as he knew he could use the clones as weapons against Big Boss.
One year later, a man known as Skull Face and his unit, XOF, captured Chico and Paz to use them as a distraction for Big Boss while XOF attacked Mother Base. Despite the fact that Big Boss and Miller escaped, the operation succeeded, as Mother Base and MSF were no more.
Nine years after the destruction of MSF and Mother Base, Big Boss had awakened from his coma. During his coma, Skull Face had gone rogue and attacked Zero. Zero created a "phantom" of Big Boss by using Big Boss's best man, who had also fallen into a coma, by giving him plastic surgery and hypnotherapy. Shortly after "Venom Snake" woke up, XOF soldiers located him and attempted to kill him. With the assistance of Big Boss, under the codename Ishmael, and former rival Ocelot, Venom Snake managed to escape from the XOF soldiers that were sent to kill him. Sometime later, Venom Snake rescued Miller in Afghanistan. When they returned to their new base, Miller vowed that everything they did would be to combat Cipher out of revenge. The war had officially begun.
During those nine years, Miller formed Diamond Dogs to combat Cipher. At some point, their comrade Huey Emmerich and a female sniper known as Quiet were tortured by Ocelot, who eventually learned that Cipher was pursuing new research in South Africa to find the missing link which would provide the materials necessary to create a weapon to surpass even Metal Gear.
By 1995, Big Boss had officially created Outer Heaven and gave control of the country to Venom Snake while Big Boss himself returned to the United States. When the Outer Heaven Uprising was formulated, he kept his status as the leader of Outer Heaven a secret to use his control of FOXHOUND to feed misinformation to the United States government while he forced Dr. Madnar to create the TX-55 Metal Gear for use against the Patriots. The Patriots used Solid Snake to stop the uprising and destroy Metal Gear, though at the time, the latter was unaware of who he was truly working for. While Snake had succeeded in his mission, killed Venom Snake, and left Big Boss for dead, the latter had actually survived, and escaped with many of Outer Heaven's citizens.
In late 1999, Big Boss became the President of Zanzibar Land, and with his most trusted lieutenant, Gray Fox, tried once again to fight the Patriots. This time, he did so by forming an army from various soldiers and war orphans from across the globe. By this point, Dr. Madnar was willing to create a more powerful version of TX-55, dubbed Metal Gear D. Snake was able to destroy Metal Gear D and gravely wound Gray Fox and Big Boss. He then left, believing that his work was done.
The Patriots later scavenged through Zanzibar Land and recovered the bodies of Gray Fox and Big Boss. The Patriots gave Gray Fox to Dr. Clark, who then resurrected him through use of a top secret government project. Instead of killing Big Boss, the Patriots put him in a nanomachine-induced coma to remain the icon for the Patriots, and to be a prisoner of Zero's will. The Patriots, for the time being, had won the war.
EVA and Ocelot, seeing how dangerous the Patriots had become, decided to form the unofficial anti-Patriot faction to kill the corrupted members of the Patriots. In 2003, EVA and Ocelot recruited Naomi Hunter, Gray Fox's adopted sister, into their organization and used her to help Gray Fox escape and kill Dr. Clark.
During the Shadow Moses Incident in 2005, Ocelot, having infiltrated Liquid's group known as the Sons of Big Boss to get the Metal Gear REX dummy warhead data for George Sears, used his torture device to kill Donald Anderson, though he covered it up as an accident. After the deaths of Dr. Clark and Donald Anderson, the Patriot AIs Zero had commissioned in the '70s and '80s took completely over.
Before the Guns of the Patriots Incident began, the AIs programmed a new strain of FOXDIE which would kill their enemies EVA, Ocelot, and Big Boss, should the latter ever wake up. They then gave it to Drebin 893 to inject into the unwitting Old Snake, who then went on to indirectly kill them.
Nine years later, in 2014, Snake and Otacon did what Big Boss could not, and destroyed the AIs along with the Patriots. When Snake attempted to commit suicide due to the new strand of FOXDIE in his body, Big Boss appeared with a vegetative Zero, and explained the history of the Patriots, claiming that the organization would not truly die until Zero himself died. Big Boss then killed Zero, finally bringing a conclusive end to the Patriots. A few minutes later, Big Boss died from the new strain of FOXDIE, thus putting an end to the war between Big Boss and Zero for good.