The original, human Zodiac was founded by Cornelius van Lunt, a New York City area businessman who started his career in legitimate real estate dealings, but who branched out into various criminal endeavors. An ardent believer in astrology, van Lunt amassed a fortune under the guidance of his personal astrologer. Van Lunt invested that fortune in the formation and outfitting of a nationwide criminal network. Van Lunt hand-picked the original eleven other Zodiac leaders, but long concealed his true identity from them beneath his zodiacal personal Taurus. Van Lunt was originally the only member of Zodiac who knew the true identities of all the other leaders. Each of the twelve leaders of the Zodiac was born under the sign of the zodiac after which he or she was named, and was based in a different American city.

None of the twelve leaders of Zodiac possessed superhuman powers, but most of them employed technology to give themselves special capabilities. Generally, the Zodiac leaders each operated independently in the city that was his or her base of operations, but they assembled for matters of collective importance. Whenever there was a vacancy in Zodiac's leadership, either by death or expulsion, the remaining leaders accepted applications for membership from criminals, who met certain qualifications, chief among which was having been born under the zodiacal sign of the vacancy. Traditionally, all of the Zodiac leaders were male except for Virgo. Following his horoscope, van Lunt relinquished control over the group and Zodiac took on a rotating system of overall leadership. Hence, leadership over the entire organization changed from month to month according to the prevalent astrological sign, and thus each of the twelve Zodiac leaders got to direct the entire organization for a month each year. Each of the twelve Zodiac leaders also commanded his or her own group of henchmen based in his or her base city.

The human Zodiac's ultimate goal was that of world economic and political domination. Zodiac intended to rule humanity just as its leaders believed that the astrological zodiac governed humanity's fate.

The first recorded activity of a Zodiac leader as a member of that organization was the unsuccessful attempt of Jacob Fury, the original Scorpio, to assassinate his brother Nick Fury, the Public Director of the international espionage and law enforcement agency SHIELD. Scorpio wielded an ankh-shaped extradimensional power object called the Zodiac Key, which was the most powerful weapon utilized by the Zodiac organization. Jacob Fury was killed after his second failure to murder his brother, and, after feigning his own death at the hands of the subversive organization HYDRA, Nick Fury, now in possession of the Zodiac Key, disguised himself as Scorpio in order to infiltrate Zodiac. At this time Zodiac was led by Aries, whose term of leadership, under the rules by which Zodiac then operated, was much longer than a single month. In the guise of Scorpio, Nick Fury captured the Avengers and summoned the rest of Zodiac to Avengers Mansion, planning to free the Avengers and have them help him capture the other eleven members. Unfortunately, the plan failed, although neither Fury nor the Avengers were seriously harmed, and Zodiac escaped, with Aries taking possession of the Zodiac Key.

Sometime later, Aries, leading a small army, succeeded in capturing Manhattan Island and sealing it off from the rest of the world within a force field. His attempt to hold Manhattan for ransom was thwarted by the Avengers and Daredevil. Aries died in an explosion in which the Key was apparently destroyed.

The Key was rediscovered, however, and Nick Fury, Daredevil, Iron Man, Madame Masque, Aquarius, Capricorn, and Sagittarius all found themselves transported with the Key to the dimension of its true owners, the Brotherhood of the Ankh. The six Earthmen were returned to Earth, but the Brotherhood retained the Key.

Van Lunt, as Taurus, became the new leader of Zodiac and recruited a new Aries and what he believed to be a new Scorpio. Actually, the new Scorpio, Jacques LaPoint, was the disguised Jacob Fury, whom the sentient Zodiac Key had recreated as an android. Taurus embarked upon a scheme to use a "Star-Blazer" device, powered by some form of "stellar energy," to kill all the people living in Manhattan who were born under the sign of Gemini as a means of displaying Zodiac's power. The Avengers thwarted this scheme and destroyed the Star-Blazer. An internal power struggle then occurred in which six of the Zodiac leaders turned against Taurus, who induced both the rebellious leaders and the Avengers into a death trap. But the dissident Zodiac leaders and the Avengers survived, and the Avengers succeeded in defeating and capturing Taurus, the Zodiac leaders loyal to him, and the dissident Zodiac leaders. The charges brought against the Zodiac leaders by the Avengers put them behind bars, but they eventually all regained their freedom by various means. It was at this point that van Lunt, who had been Zodiac's financier from the beginning, instituted the system of monthly rotating membership.

Jacob Fury, once again in possession of the Zodiac Key, used it to create the first version of his android Zodiac, which was defeated by the Defenders and Moon Knight.

The human Zodiac had been greatly weakened in power by the capture and temporary imprisonment of its leaders. Van Lunt, as Taurus, planned to compete in certain criminal activities with one or more of the New York City-based "families" of the criminal organization called the Maggia. Learning of van Lunt's intentions, the Maggia acquired the services of the android Taurus and sent it to wreak destruction at van Lunt's new base of operations. Unable to defend himself against the android, van Lunt contacted an associate who hired James Rhodes, the second Iron Man, to defend van Lunt's property. Although Rhodes defeated the android, thereby saving van Lunt's life, van Lunt regarded Iron Man as a threat to Zodiac's future plans. Deducing Iron Man was Rhodes, van Lunt contacted Aries and Aquarius and sent them to assassinate him. Aries and Aquarius failed, however, and were briefly imprisoned.

Months later, Jacques LaPoint revealed himself as Jacob Fury at a meeting of the human Zodiac's twelve leaders. The other eleven members of the latest version of the android Zodiac broke in, and they and Jacob Fury murdered all of the human Zodiac leaders except for van Lunt, who escaped. Van Lunt sought help against the android Zodiac from the West Coast Avengers. The android Zodiac was seemingly destroyed shortly afterwards, but the sentient Zodiac Key intends to resurrect Jacob Fury, who will undoubtedly recreate the rest of the android Zodiac. Van Lunt escaped the Avengers and planned to form a new human Zodiac. But the Moon Knight found van Lunt and battled him aboard a plane in flight. Van Lunt died when the plane crashed, but the Moon Knight escaped to safety.

FIRST APPEARANCE: (Zodiac as an organization) Avengers #72
FINAL APPEARANCE: (death of ten members of human Zodiac) West Coast Avengers#26