When Kaiba left Kaiba Corp after being defeated by Yugi, the Big Five conspired with Maximillion Pegasus to take over Kaiba Corp, and have Kaiba killed. Kaiba survived, however, but Pegasus defeated him in a duel and trapped his soul inside a card. The Big Five watched the duel between Yugi and Pegasus, planning to broadcast it if Pegasus won. However, Yugi won instead.
Upon return to Kaiba Corp, Kaiba fired the Big Five, but they told him they were pretending to work for Pegasus. They also finished Kaiba's virtual reality game, so he entered it, but they set a trap inside it for him to kill him. Kaiba's brother Mokuba asked Yugi and his friends to help. Soon, Yugi, Kaiba, Joey, and Mai faced off against the Mythic Dragon, which the Big Five themselves seemed to take the form of (a five-headed dragon). Joey, Mai, and Mokuba were all killed by the Mythic Dragon , and Kaiba and Yugi worked together to summon Master of Dragon Soldier, which destroyed Mythic Dragon, trapping the Big Five in the virtual world.
The Big Five remained trapped in the virtual world so long that their bodies were destroyed. They soon came across Noah Kaiba, the son of Kaiba's wicked stepfather Gozaburo Kaiba, and joined forces with him as they shared a common enemy in Kaiba. When Yugi, Joey, Téa, Tristan, Serenity, Duke, Kaiba, and Mokuba entered the virtual world, Noah and the Big Five separated them for the Big Five to duel them and steal their bodies. They dueled using a deck master system, with the Big Five in the forms of their own deck masters. Gansley was Deep Sea Warrior, Crump was Nightmare Penguin, Johnson was Judge Man, Nesbitt was Robotic Knight, and Lector was Jinzo.
Yugi defeated Gansley, Téa defeated Crump, and Joey defeated Johnson. Tristan, Duke, and Serenity dueled Nesbitt at once. Although they were able to defeat him when Serenity attacked him, Tristan's life points went down to zero during the duel, so Nesbitt stole his body and digitized him into a robot monkey. Kaiba defeated Lector. Nesbitt kidnapped Mokuba and took him to Noah to brainwash him.
Gansley, Crump, Johnson, and Lector returned to chase Joey, Duke, and Serenity and steal their bodies. Crump and Lector got in a fight over who gets to choose first. Noah, however, recalled them and chastised them for cheating. He then sent them to duel Yugi, all in Tristan's body. They dueled Joey, taking it in turns to possess Tristan's body to duel, rotating their deck masters as well. Lector did most of the duel, but they were defeated when their deck master was destroyed. Again, they tried to steal the gang's bodies by force, but Noah recalled them again, and permanently trapped them each in an isolated corner of the virtual world.
The Big Five were never seen again following their imprisonment, but did not remain there forever; they were killed when Noah blew up the fortress that the virtual world was stationed in, deleting the virtual world and anyone in it at the time, including Noah and Gozaburo themselves.
In the manga, after the Pegasus arc, the Big Five are fired and are never seen again, as both virtual world arcs are filler.
- In LittleKuriboh's parody series, Yu-Gi-Oh! the Abridged Series, in addition to their roles in the original anime, the Big Five are also depicted as being board members of 4Kids Entertainment, which is depicted as a ruthless organization. After their diabolical plan to cancel Yu-Gi-Oh! the Abridged Series succeeds at the end of Season 2, they plan with Noah on how to deal with Yugi and his friends, setting up Season 3 . The Big Five sound relatively similar to how they do in the anime. They are also voiced by different voice actors than LittleKuriboh. Despite 4Kids's censoring death, the Big Five do not have a problem with killing people themselves, as they have attempted to kill Kaiba multiple times, and discuss killing Yugi and his friends in ways similar to their deck masters. They also retain much of their original personalities; Crump is obsessed with penguins just as much, if not more, as he is in the anime. In Season 3, Gansley claims that they have new voices ; Gansley's voice at least does sound different. They also make their entrance similar to Team Rocket.
- Two of the Big Five, Johnson and Crump, share their names with the only two X-Nauts from Paper Mario: The Thousand-Year Door who have names. Lord Crump is the general of the X-Nau, and Johnson is a regular X-Naut referred to once by Crump.
- Lector takes the form of Jinzo in the virtual world. Jinzo's mask resembles that of Hannibal Lecter, which may be where Lector gets his name.
- The Big Five are not the only evil team of five to start out shadowed and later be revealed. In Dragonball Z, the Ginyu Force are shadowed as they leave Planet Frieza for Namek, and are not fully seen in color until they arrive and strike their poses. Are all shadowed, until later Mimet is revealed. The remaining three witches are fully seen in color in their respective episodes, but only last one episode before each is killed.
- Three of the Big Five resemble figures that are evil in Family Guy. Gansley resembles Jerry of the El Dorado Cigarette company in the episode Mr. Griffin Goes to Washington, the leader of the FCC, which censors everything in PTV, resembles Nesbitt, and in the episode FOX-y Lady, the leader of the Fox channel , whom Brian says is evil, and is later proved to be right, resembles Johnson. This is like a coincidence, however. This is also comparable to the Abridged Series, where they are members of 4Kids, who are portrayed as evil in this series.