The wielder of these great cards is able to acquire the title of "Duel King," but in the wrong hands, they are capable of causing legitimate injury or even death. Using counterfeits of the "God" cards also proved to be deadly, as Marik Ishtar found out when his Rare Hunters were testing counterfeited copies of "The Winged Dragon of Ra", some ended up being crippled, some lost their minds, and some even died the moment the card was played. Marik came to the conclusion that the "Gods" respond to the strength of heart of the Duelists, of which none of the members of the experimental group had, and to this end, he gave Odion a copy of "Ra", reasoning that he would be able to control it due to his past as a servant of the Tomb Keepers. Unfortunately, this proved to be incorrect, resulting in both Duelists being struck down.
Marik was able to acquire "The Winged Dragon of Ra" and "Slifer the Sky Dragon", but Ishizu was able to protect "Obelisk the Tormentor". She gave the card to Seto Kaiba, and requested that he host a Dueling tournament to lure Marik and his Rare Hunters to the city, bringing the other "God" cards with them. Kaiba, intent on claiming the cards for himself to secure his title as the strongest Duelist, agreed and hosted the Battle City tournament. During the tournament Marik revealed to Yami Yugi the "God" cards and that the Millennium Puzzle were needed to unlock his lost memories. Marik used "Slifer the Sky Dragon" against Yami Yugi through Strings, but Yami Yugi was able to defeat "Slifer" and took it for himself in accordance with Battle City's ante rules. Kaiba reveled in the power of "Obelisk the Tormentor" after testing it against his own Deck, and he used it throughout the tournament against Koji Nagumo and several Rare Hunters, including Lumis and Umbra.
During the tournament quarterfinals, Yami Yugi used "Slifer" for the first time to defeat Yami Bakura. Marik had placed a copy of "The Winged Dragon of Ra" in Odion's Deck without his knowledge, telling him that usage of the card against Joey Wheeler was needed to prove to those watching that Odion was Marik, as Marik was keeping his identity a secret. After Odion was struck down by "Ra's" rage for using a counterfeit of its card, Marik was taken over by Yami Marik, who Dueled Mai Valentine in the next round. Mai successfully took "The Winged Dragon of Ra" from Yami Marik's Deck with "Amazon Chain Master" and Summoned it, but was unable to read the hieratic text on the card one needed to recite to control it. On his next turn, Yami Marik did so himself and took back control of "Ra" to win the Duel.
In the final round of the quarter-finals,Kaiba faced Ishizu who had entered the tournament to save her brother and reclaim "Obelisk" from Kaiba. Using her Millennium Necklace to foresee Kaiba's moves, Ishizu allowed him to Summon "Obelisk" with the intent to destroy it with "Blast Held With a Tribute", but a vision from Yami Marik's Millennium Rod convinced Kaiba to win using his "Blue-Eyes White Dragon", thwarting Ishizu's strategy. In an unofficial fifth Duel later that night, Yami Bakura Dueled Yami Marik, and Bakura seized "The Winged Dragon of Ra" with a combination of "Dark Designator" and "Exchange", and with the help of the spirit of the original Marik was able to Summon and control Ra. However, Yami Marik sapped "Ra's" ATK to 0 with "Joyful Doom" and when Bakura abandoned "Ra" later in the Duel, Yami Marik revived it with "Monster Reborn" and revealed its secret abilities Instant Attack and Point-to-Point Transfer to win the Duel.
The Egyptian God Cards did not appear during the Virtual World arc since the Big Five had the cards forbidden from their database that was used to choose a player's Deck.
Marik and Joey Dueled in the semi-finals, and Yami Marik unveiled "Ra's" Phoenix Mode, burning Joey and wounding him so badly he fell unconscious and was unable to finish the Duel. In the next Duel, Kaiba and Yami Yugi faced each other and eventually both got their "God" cards on the field. After several turns of the two weakening and powering up the two cards, they equaled at 4000 ATK and destroyed each other, the clash triggering a vision of the Duel between Priest Seto and Pharaoh Atem in Ancient Egypt, and a vision of their two Gods petrified. Yami Yugi was eventually able to win the Duel with "Dark Paladin", claiming "Obelisk".
In the final Duel against Yami Marik, Yami Yugi used both "God" cards to battle him, but it was revealed "Ra" was stronger than both the other "God" cards and it destroyed "Slifer" with ease and eventually forced Yugi to sacrifice "Obelisk" to survive. Nonetheless, Yami Yugi eventually won by using "Ragnarok". In the manga, Yugi used "Dimension Magic" to have two Magicians on the field, then the second effect of "Dimension Magic" makes Yugi combine the attacks of his two Magicians and destroy "Ra" in battle. As Yami Marik was fused with "Ra" at the time, this allowed Marik to regain control of his body from his dark half. Marik surrendered the Duel to Yugi, and gave him "Ra".
In the Waking the Dragons season, Yami Yugi attempts to use the "God" cards to unlock the Tablet of Lost Memories, but it is iced over by the power of Dartz, preventing him from regaining his memories. The "God" cards are later stolen when Solomon Muto is caring for them by Dartz's underlings. "Obelisk" was briefly used by Gurimo against Yami Yugi and though it was successfully controlled by "The Seal of Orichalcos" the combination caused Gurimo to suffer discomfort. After Gurimo's defeat, the God cards were taken to Dartz's temple, where they were drained of their energy to fuel the Great Leviathan. They are retrieved at the end of the season and empowered with the light of Dartz's captives to battle the Great Leviathan in physical form, defeating it decisively.
In the Memory World arc, Yami Yugi uses the "God" cards to enter the world of the Pharaoh's memory. Here, acting as Atem in what is actually an RPG-type Shadow Game orchestrated by Yami Bakura, Yami Yugi battles Thief King Bakura and his Diabound with the "God" monsters one by one. "Slifer" is destroyed by Diabound, resulting in Diabound gaining its power, but "Ra" successfully destroys Diabound. However, as the Summoning of "Ra" was as a result of outside interference from Yugi, Yami Bakura used his ability as a player of the Shadow RPG to rewind time and prevent the Summoning of "Ra".
Yami Yugi later Summons the Gods to battle Zorc Necrophades, apparently defeating them, but Zorc petrifies the Gods, badly injuring the Pharaoh. Upon learning his name, Yami Yugi/Atem uses it to merge the "Gods" into "Holactie the Creator of Light", destroying Zorc and winning the Shadow RPG. Afterwards Yami Yugi used the "God" cards again against Yugi Muto in the Ceremonial Battle, Yugi destroying the cards by turning "Slifer's" effect against the "God" cards with "Magnet Force" in the manga, Atem only Summoned Obelisk, but it was weakened, and Yugi's "Silent Swordsman" was strengthened, making both their ATK 2500, then, when Obelisk attacked, they were both destroyed. In the Duel's final move, Yami Yugi attempts to revive "Slifer" with "Monster Reborn", but Yugi had foreseen this and sealed "Monster Reborn" with "Gold Sarcophagus", allowing him to win the Duel. The three "God" cards were then lost forever when the tomb collapsed, burying the seven Millennium Items along with the cards when Atem left for the afterlife.