The first-known group was a criminal organization founded by Taurus, a corrupt businessman named Cornelius Van Lundt who sought personal power and dominance of the masses, using astrology to guide his and the Zodiac's machinations. Leadership of the Zodiac would fluctuate between the members, based on the "dominance" of their calendar sign. Various Zodiac members would often attempt plots on their own, independent of the main body of the Zodiac, notables including Aries, Capricorn, and Scorpio. As a team they first fought the Avengers.
Scorpio, who had engaged his brother Nick Fury in a series of criminal efforts years before the debut of the Zodiac, left the original Zodiac and constructed his own team with Life Model Decoy technology stolen from S.H.I.E.L.D. Scorpio eventually killed himself after the collapse of his schemes. His weapon an item known as the " Zodiac Key", empowered by a group of extra-dimensional mystics called The Brotherhood. transferred his intellect into a Life Model Decoy duplicate, granting him a second life. This "reborn" Scorpio would construct various android incarnations of the Zodiac. Zodiac-themed villains would come into conflict with various superheroes, among them Daredevil, Ghost Rider, Iron Man, S.H.I.E.L.D., She-Hulk, and most notably, The Avengers.
Fury's android cartel eventually infiltrated and destroyed Van Lundt's original Zodiac; only a few members are known to have survived. Fury/Scorpio claimed that the Brotherhood had long-controlled the Zodiac and intended him to serve as its master. Fury and his machines were later deactivated and the key retaken by the mystics.
Since then, many different cartels have manifested, each with its own general trappings and motivations, all employing at least a single costumed enforcer, and all motivated by emulation of the zodiac calendar. One Zodiac, made up of soldiers in Romanic dress, occupied New York shortly before Onslaught's devastation of the city. This Zodiac was led by a single agent, Libra. Later, a fully costumed cartel became active in Canada. They were opposed by the then-current incarnation of Alpha Flight, and then slaughtered by the mutant task force Weapon X. Shortly before the disbanding of the original Avengers charter, a new Scorpio, armed with a copy of Fury's key, battled the team. Scorpio reported to a shadowy group of men in a boardroom-style headquarters, these men were identified as the "actual" Zodiac, Scorpio serving as a colorful facade/agent. Since then, Scorpio has apparently recruited a new public Zodiac team, which attacked the UN but was stopped by the Young Avengers.
A new Zodiac team was fighting the Initiative heroes, the New Warriors came to help them out. Not all twelve signs were there though. Three were not in the line-up: Aquarius, Capricorn and Gemini. Longstrike of the New Warriors is killed, in front of her teammates, by Cancer in this same issue.
An anarchist later murdered all the members of the Zodiac in order to use their name for himself. Alongside a group of villains which included the Clown, Death Reaper, Manslaughter Marsdale, Trapster and Whirlwind, they formed a post-modern incarnation of the team. They disbanded at some point, although the anarchist is still active and calling himself Zodiac, most recently as a benefactor for the Young Masters.
The new Zodiac has since formed who's powers are based on their signs. They were brought together by Thanos and John King.