The characters that would form the Global Guardians first appeared in the Super Friends comic book series. The first were introduced in a story (in Super Friends #7-9) in which an alien villain called Grax (an old Superman foe) planted bombs on Earth's seven continents to destroy it. Thanks to a warning from the Wonder Twins (in their first comic book appearance) the Justice League discovered the plan in time and recruited the heroes of the countries affected to find the bombs before they exploded.
These international heroes would later appear in other issues of Super Friends. However, it wasn't until DC Comics Presents #46 (June 1982) that they were introduced as a team, in a story in which they helped Superman to stop an evil Atlantean sorcerer named Thaumar Dhai. This is also considered to be these characters' first canonical appearance in the DC Universe.
After Crisis on Infinite Earths, it was revealed that the Global Guardians had been gathered together by Doctor Mist to serve as the enforcing arm of an international organization called "The Dome", which had been created by the Treaty of Rome in 1957 to help organize the efforts of superheroes across the globe as an international police organization.
Prior to that, in the early 1950s, several international heroes who had been the beneficiaries of the Justice Society of America's kindness during and after World War II, had banded together in an informal "Club of Heroes". They were integrated in the Global Guardians after its foundation. (Batman's butler Alfred Pennyworth sends Christmas cards to the currently surviving members).
This original Global Guardians were based in a United Nations-financed headquarters building also called the Dome located in Paris. The original team was also funded by Doctor Mist and administrated by a woman called Belphegor who was gifted with psychic powers. Many of the Guardians individually assisted other international heroes during the Crisis on Infinite Earths crossover and once teamed up with Infinity, Inc..
The Guardians eventually lost their UN funding to the Justice League, and the Dome was ordered to close, in part due to the political machinations of their enemy, Dr. Klaus Cornelius. Some of its members left the team to join the League, notably Green Fury and Icemaiden (who changed their names to Fire and Ice). The others went freelance.
Part of the team was brainwashed by the Queen Bee of Bialya and were directed to battle the Justice League. Fain Y'onia, an ancient foe of their leader, Doctor Mist, caused the deaths of Bushmaster and Thunderlord and depowered others. The surviving Guardians would continue to meet in the Dome's Headquarters, which was formerly located in Europe but is now in the Pacific.
In a story in the JLA Classified series, some of the Guardians were seen to have joined the Ultramarine Corps.
In 2006, as part of the events of One Year Later, in Green Lantern #10, the Global Guardians are shown regrouped, apparently led by former New Guardian Jet. They attempt to recruit the newest Crimson Fox. When she declines, they say she has no choice. Crimson Fox is later seen publicly voicing the opinions of the Guardians, among them a hatred for Hal Jordan. It is eventually revealed that they are being telepathically controlled by the Faceless Hunter in his attempts to capture Green Lantern. They are defeated and freed from the alien's control.
In World War III, in 52 week 50, the Global Guardians assist the Marvel Family in an attack on Black Adam but were all easily and brutally defeated by the enraged villain.
In the 2009 Justice League: Cry for Justice series, it was revealed that members of the Global Guardians had been targeted and killed by Prometheus, including Tasmanian Devil, Gloss, Sandstorm and Freedom Beast.