The heroine of the series is the eponymous character, Cybersix, a leather-clad artificial human superhero who by day operates behind the guise of a male high school literature teacher, and by night battles the monstrous biological weapons of her creator. She is aided in her adventures by her younger brother Cyber-29, who is reborn in the body of a black panther known as Data 7. The extended cast includes Cybersix's colleague and love interest Lucas Amato, as well as other supporting characters.
In 1995, the comics were adapted into a poorly-received live-action television series, and again in 1999 into a much more successful thirteen-episode animated series by TMS, with positive critical reception from sources like the Pulcinella Awards, which first aired in Canada on Teletoon and was later dubbed in several other countries.
Dr. Von Reichter, a member of the SS and the Nazi party, is an expert in genetic engineering. He initially began his work in concentration camps during World War II, implanting cybernetic organs in the bodies of dead prisoners in an attempt to bring them back to life to serve in the Führer's army. However, the Allied forces intervened to defeat the Nazis, so he fled to South America where he once again continued his sinister experiments.
From one of his experiments emerged the Cyber Series — artificial humanoids possessing superhuman strength and agility. But something was amiss: The 5000 original Cybers, engineered to be the perfect servants, mimicked human emotions too closely, displaying free will of their own. When they began disobeying their creator, Von Reichter ordered all of the Cyber Series to be destroyed. By this time, Cyber-29 had already died in a playtime accident when he fell from a cliff, but Von Reichter managed to transfer the dead child's brain into the body of a panther to be reborn as Data 7. Cybersix was the only true Cyber to survive the massacre, escaping with the help of a black slave who hid her away in a fishing village. When the slave was later interrogated and killed by Von Reichter, Cybersix escaped once again and made her way to the fictitious city of Meridiana, where she adopted the identity of a boy killed in a car wreck, Adrian Seidelman, and now battles her evil creator and his minions.
Like all of Von Reichter's creations, Cybersix depends on a mysterious life-giving fluid called "sustenance". When her supply ran out, she was forced to prowl the city in search of other creatures of Von Reichter's making, such as Frankenstein-like Fixed Ideas or the more human-like Technos, to kill them and take their sustenance to survive. Almost by accident, she became a superhero by defending the people of her city from Von Reichter's malevolent plans, often carried out by his cloned "son" José. Along the way, she meets the resurrected Data 7, as well as a young boy named Julian, and falls in love with biology teacher/reporter Lucas Amato.
Four special-edition Italian Cybersix issues were also released, in addition to another six documenting Volumes 1 to 18. The first book of the special edition comics had two possible cover designs.
There were five main cast members who voiced Cybersix. Cathy Weseluck performed the dual role of Adrian Seidelman and Cybersix. Michael Dobson performed the voice of Lucas Amato. Andrew Francis played Julian, while Alex Doduk and Terry Klassen voiced José and Von Reichter, respectively. Additional voices were provided by Janyse Jaud, Brian Drummond, Chantal Strand, and L. Harvey Gold.
Along with the background music, several elements of the cartoon's visual design hint that Meridiana is modeled after Buenos Aires, teeming with decorative sculpture throughout the metropolis, numerous outdoor markets and open-air cafés.
Cybersix's outfit of black bodysuit, high heels, hat, cropped gloves, and cape with red lining was taken from a Techno prostitute in the comics, while its origin is never fully explained in the animated television series.
Some of the more mature story elements, such as José and Von Reichter's Nazi background or Cybersix's youth, are not openly revealed in the animated series, but are suggested through dialogue, flashbacks, or visual clues, such as the military-style goose-stepping that both José and Von Reichter engage in.
The live-action series was heavily toned-down from the comics. Violence was reduced, and mentions of sex and drugs were absent.