The series starts with Snake Eater, set in the 1960s. Naked Snake is sent into the Soviet Union to rescue a Russian scientist from Colonel Volgin, a KGB hardliner plotting a coup against Nikita Khruschev with an experimental nuclear weapon known as the Shagohod. Over the course of the mission, Snake is betrayed by his mentor, The Boss, and an American-made tactical nuclear weapon is set off. Faced with the prospect of nuclear war, Khruschev gives the CIA a chance to prove their innocence, and Snake is sent back in to stop Volgin, destroy the Shagohod, and kill The Boss. Although he succeeds, he is deeply disturbed by this turn of events as The Boss points out that Snake will kill her because it is politically convenient for Washington. If yesterday's enemies are tomorrow's friends, then everything a soldier believes in is subverted and sacrificed. The Boss encourages Snake to fight for something he believes in, not what a politician tells him is worthwhile.
For his efforts, Snake is awarded the titled "Big Boss", but leaves the CIA shortly thereafter. He disappears for several years, re-emerging in South America during the events of Portable Ops, where he is involved in an insurrection led by Gene, a rogue soldier who hijacks a nuclear launch platform code-named Metal Gear RAXA. Snake prevents Gene's uprising, but Gene's idea of a soldier's paradise called "Army's Heaven" stays with him. With allies from the incident, Snake forms Militaires Sans Frontieres ("Soldiers Without Borders"), a mercenary unit that is a representation of The Boss' will, where soldiers, not governments, choose their own battles.
Peace Walker takes place in 1974, and sees MSF employed to investigate suspicious activity in Costa Rica. Snake is hesitant to do so because it means getting involved in Cold War politics and because he knows that his employer works for the KGB, but accepts when he hears an audio recording of The Boss' voice dated after her death. Snake finds that a rogue CIA operative has been using Costa Rica to develop Project Peace Walker, an automated nuclear launcher with an artificial intelligence modelled on The Boss. The CIA intend to use Peace Walker to end the Cold War by simulating a nuclear strike on the United States and using Peace Walker to retaliate, proving that nuclear deterrence is a myth. Snake succeeds in stopping Peace Walker, and in doing so, makes his peace with killing The Boss. However, MSF is infiltrated by Paz, a teenage girl working on behalf of someone called Cipher, in an effort to get MSF declared a terrorist organisation. Paz is stopped and falls from MSF's Mother Base, where she is missing and presumed to be dead.
Ground Zeroes takes place two weeks later, with MSF learning that Paz survived and was captured by the Americans. Chico, a boy living with MSF, mounted his own rescue attempt, but was similarly caught. Snake goes in to rescue them as he believes that Paz is conflicted and might switch sides to MSF; as for Chico, he is an innocent. Snake also knows that Paz works for Cipher, and so Cipher has as much to lose as MSF do, and so by saving her, he gets a bargaining chip to work with. At the end of the game, Mother Base is destroyed by the XOF Unit (a dark version of Snake's original FOX Unit) and Snake falls into a coma.
The Phantom Pain takes place in 1984, with Snake awaking from his coma and going out to find the people responsible for the destruction of Mother Base and the deaths of his men.
The game then switches protagonists for the original Metal Gear, with Solid Snake, a rookie agent, sent into a fortress called Outer Heaven (remember Gene's "Army's Heaven"), which has acquired a Metal Gear prototype, a walking, nuclear-equipped battle tank. Snake infiltrates the base and ends the threat under the direction of Big Boss - Naked Snake - only to discover that Big Boss is the leader of Outer Heaven. Metal Gear 2: Solid Snake follows largely the same plot, with Solid Snake going into the rogue Zanzibar Land to stop another Metal Gear prototype. He also finds that Big Boss has survived.
Metal Gear Solid skips ahead in time, and sees a retired Solid Snake recalled to active duty to infiltrate the Shadow Moses nuclear disposal facility in Alaska, which has been overrun by the FOXHOUND unit, led by Snake's twin Liquid Snake. Snake discovers that he, Liquid, and an unnamed third man are actually clones of Big Boss, born as part of "Les Enfants Terrible" ("The Terrible Children"), a secret project to clone Big Boss. Liquid and FOXHOUND demand Big Boss' body, wanting to use his genetic material to re-engineer their bodies and escape a destiny chosen for them by politicians. They have acquired another Metal Gear prototype, Metal Gear REX, and are pointing it around and threatening people with it. Solid destroys REX, defeats Liquid, and returns to retirement, deciding that although he is a clone of Big Boss, he is free to live his life on his own terms.
Sons of Liberty takes place four years later, with Solid Snake working for Philanthropy, an anti-Metal Gear organisation. While acquiring evidence of a new Metal Gear model, Metal Gear RAY, Snake witnesses Revolver Ocelot - a recurring character from Snake Eater and master of the quintuple-cross - steal RAY and sink the tanker transporting it, while Snake and Philanthropy taking the blame. Two years later, a group of terrorists called "Dead Cell" take control of the Big Shell offshore clean-up facility that was constructed to clean up the damage caused by the tanker sinking. Raiden, a rookie agent, is sent in to stop the threat. There he meets Snake - masquerading as a Navy SEAL - and the two encounter Solidus Snake, the third clone of Big Boss, who is better-known as George Sears, former President of the United States. Solidus reveals that democracy is a sham, carefully co-ordinated by a sinister conspiracy known as "the Patriots". The Patriots are using Big Shell as a cover to build Arsenal Gear, a mobile fortress managed by a group of artificial intelligences tasked with controlling human development by filtering out information on the internet - kind of like genetic engineering, but managing data rather than genes. Solidus plans to detonate a nuclear weapon over New York City to break the Patriots' hegemony. Ocelot, an agent of the Patriots, steals data from Arsenal Gear; Solid Snake gives chase while Raiden confronts Solidus.
Solid Snake - now known as Old Snake - returns as protagonist of Guns of the Patriots. Despite his best efforts, the world is dominated by war, to the point where war is the main pillar of the global economy. Snake tries to stop Ocelot from hijacking the network controlling the world's armies. It is revealed that the Patriots are led by Major Zero, Naked Snake's commanding officer from Snake Eater, and that everything that has happened has been a result of an ideological fall-out between Naked Snake and Zero as to how to enact The Boss' vision of a world where soldiers are free to fight on their own terms. Solid Snake and Ocelot find themselves in a similar position - both want to destroy the Patriots, but have very different ideas on how to go about it - and it is implied that the cycle could start all over again. Big Boss is revealed to be alive, having spent decades in a forcibly-induced coma; he awakens and shuts off the life support system keeping the vegetative Major Zero alive before dying of a genetically-engineered virus. With Ocelot dead, the conspiracy over and the Patriots' network finally shut down, the world is free again, and Snake goes on to live his life for the first time.