The events of "One More Day" began in Amazing Spider-Man #544, where Peter Parker's Aunt May is shown slowly dying from a gunshot wound sustained during the events of Civil War and "Spider-Man: Back in Black". Peter is forced to ask Tony Stark for financial assistance, and then seeks counsel with Doctor Strange. The latter informs Peter that he can do nothing to grant Aunt May her life back. However, he helps Peter seek the aid of several others including Doctor Doom, the High Evolutionary, Reed Richards, and Doctor Octopus. Peter attempts to go back in time using a magic spell without Strange's approval, harming himself in the process. Strange heals his wounds and sends him on his way, encouraging him to be by his Aunt's side at her death.
On his way to the hospital, Peter is confronted by a little girl, who says she holds the answer to his problem. He talks to the little girl, who runs off. While pursuing her, Peter encounters a group of men; a woman in red informs him these are alternate versions of himself, from alternate timelines where he never became Spider-Man. The woman in red transforms into the demon Mephisto, who tells Peter he can save Aunt May. As payment, Mephisto wants not Peter's soul, but his marriage to Mary Jane. Peter and Mary Jane are given until midnight the following night to decide their answer and, after several hours agonizing over the choice, they agree to the deal, as long as knowledge of Peter's secret identity is erased from the world. Mary Jane also whispers to Mephisto another, unspecified offer in return for Mephisto putting Peter's life back exactly how it was and "[giving] him a chance at happiness." Finally, Mephisto reveals to the couple that his disguise as the little girl was in fact their future daughter, but she will never exist because of their decision. This future daughter is not to be confused with May "Mayday" Parker (Spider-Girl). May "Mayday" Parker is the baby that Peter Parker and Mary Jane had at the end of the Clone Saga from the 1990s and would grow up to be Spider-Girl if Norman Osborn never killed her.
Mephisto then changes history so that Peter and Mary Jane never married, and no one remembers whose face is underneath Spider-Man's mask. Peter wakes up alone in bed, once again living with Aunt May. He attends a party being held for his best friend Harry Osborn (previously thought to have died in Spectacular Spider-Man #200), who introduces Lilly Hollister and Carlie Cooper. Peter glimpses Mary Jane sadly leaving the party. The guests all toast to a "Brand New Day."