Mephisto has been known to share stories of himself and other Hell-lords, inspiring writers like John Milton and Johann Wolfgang von Goethe to pen Paradise Lost and Faust respectively. The devil surely had other secret activities going, but more recently he made a deal with Cynthia von Doom to give her the power to avenge her people in Latveria. He agreed, but she was killed for her actions. Her soul went to Mephisto's realm where he tortured her. However, her son Victor von Doom, AKA Doctor Doom, grew up to become the Latverian leader. He and Mephisto agreed to battle each year for Cynthia's soul.
Mephisto made a deal with Howard Stark that would result in him acquiring the soul of Tony Stark, the boy who would become Iron Man. Some years later, he made a similar deal with Norman Osborn, AKA Green Goblin, regarding the soul of his son, Harry. A few decades later, during the Silver Surfer's first time exiled on Earth, Mephisto noted the pure goodness of his soul and attempted to corrupt the Sentinel of the Spaceways. However, the former Herald of Galactus persevered and even refused the return of his homeworld Zenn-La and his love Shalla-Bal. The devil found himself similarly fascinated by Thor, but has not been able to hold his Asgardian soul for long.
In an effort to draw power from more souls, Mephisto worked with Pluto, Ahpuch, Ereshkigal, Hela, Yama, and Seth to permanently connect their hells. However, all of that dark energy unleashed the Demogorge who destroyed the lords. Thor managed to convince the primal entity to cease its attack and return those he had already destroyed to their previous states, including Mephisto.
The Hell-lords united once more in an attempt to further weaken the fabric of reality through their pawns the Six-Fingered Hand, a group Mephisto had helped start centuries prior, posing as Maya. When the others found out about Mephisto's secret involvement with the group, they removed their power from the other members of the Six-Fingered Hand and went their separate ways.
In an attempt to capture the souls of Reed Richards, AKA Mister Fantastic, Susan Storm Richards, AKA Invisible Woman, and their son Franklin, Mephisto utilized the power of the Dire Wraiths' planet. However, Franklin proved so powerful that he managed to actually destroy Mephisto, sending ripples through his hell dimension which allowed the captive Topaz to escape. Mephisto did not stay gone for long, though, as he was soon reborn from the evil in humanity's hearts. However, his own soul had been split into six pieces. He manipulated Martin Preston, AKA Master Pandemonium to acquire these shards for him, two of which had been unknowingly used by Wanda Maximoff, AKA Scarlet Witch, to create her children with the Vision, Tommy and Billy who would become known as Speed and Wiccan respectively.
In an effort to destroy the Beyonder (later Maker) Mephisto captured the being's incredible, reality-warping energy and created the Beyondersbane and employed the efforts of 99 Super Villains known as the Legion Accursed until the machine overloaded. Mephisto then bet the Beyonder that his champion–Spider-Man—would resist the Beyonder's challenger–Zarathos—to stay pure of soul. The web-slinger continued putting others ahead of himself and convinced the Beyonder of humanity's potential. Mephisto needed this victory so that the Earth could continue providing him with souls, including ones like Peter Parker's, which would be so much more powerful if they could become corrupted.
After a battle with Hela, who briefly managed to usurp many of Mephisto's souls, the demon found himself visited by Doctor Doom and Dr. Stephen Strange, AKA Doctor Strange, who were after Cynthia von Doom's soul. She refused her son's ploy to have the Sorcerer Supreme duped into taking her place, thus redeeming her soul. During the ensuing battle between the earthly doctors and Mephisto, Cynthia's bonds were broken and she escaped.
Another human, Baron Karl Mordo, AKA Baron Mordo, caused more trouble for the demon when he sold his soul to both Mephisto and Satannish. Doctor Strange got involved and managed to cease hostilities between the two. This conflict also introduced Strange to Mephista, the devil's daughter.
Mephisto thought that he had finally acquired the Silver Surfer's soul after managing to capture Galactus' then-current Herald Frankie Raye, AKA Nova. He agreed to give the demon his soul, but Galactus himself traveled to the hell dimension and threatened to devour it if Mephisto did not cancel the deal with the Surfer.
Having gathered the other pieces of Mephisto's soul, Master Pandemonium finally tracked down Billy and Tommy Maximoff. Because Scarlet Witch's magic kept the boys in existence, the disruption of that energy led to the devil's brief dissipation. This absence lead to Mephisto's son Blackheart beginning his own machinations, though he was often guided by his father, whether he knew it or not.
In an attempt to attain Loki Laufeyson, AKA Loki's soul, Mephisto made a deal with the trickster himself, which was mutually beneficial, for a time. Later, Mephisto ingratiated himself to Thanos during the Mad Titan's search for and acquisition of the Infinity Gems. The demon claimed to have secret knowledge of how they worked that could prove useful. Once again, he was acting in existence's best interest as that's where his power came from.
Relations between father and son continued to be rocky as Blackheart attempted to get James Howlett/Logan, AKA Wolverine, Danny Ketch, AKA Ghost Rider, and Frank Castle, AKA the Punisher, to kill Mephisto. The son also facilitated the escape of Simon Williams, AKA Wonder Man, who the devil had under his sway.
Mephisto once more got involved in reality-threatening cosmic problems when the Goddess threatened to cleanse all life from existence. He worked with Adam Warlock and Thanos to stop her machinations. He also allied himself with the Avengers to reacquire souls stolen from his realm by Satannish. He killed Bobbi Morse, AKA Mockingbird–or rather the Skrull impersonating her–when the targets were destroyed in the process.
Blackheart finally succeeded in killing his father after covering his blade in the blood of innocent Lucy Crumm. The son finally usurped his father's throne, but during this time, Thor did manage to free Loki's soul, which had been kept in Mephisto's realm. Blocked from heaven and hell, Mephisto existed only as a shadow on Earth, able to manipulate some souls to a small extent. An attempt to use the Silver Surfer to return failed. However, Noble Kale's spirit managed to topple Blackheart before Mephisto took his rightful place once more.
In his efforts to gain control of T'Challa', AKA Black Panther’s soul, Mephisto established an alliance with Achebe. The Black Panther responded by turning the goodness of the past Panthers' souls against the demon. After attacks from the Thunderbolts, Dormammu, and Archenemy, Mephisto managed to re-establish control over his realm, though a subsequent attempt to destroy mutants across all realities failed. However, he did finally managed to make a deal with Spider-Man. The hero desperately wanted to save his dying aunt May Parker, AKA Aunt May. The devil agreed to help, but only if it would totally negate his marriage to Mary Jane Watson. Parker agreed and everyone forgot they were together. This agreement also led to the general public forgetting the hero's true identity as Peter Parker.
Mephisto and Amara Aquilla, AKA Magma, began a romantic relationship after she and the New Warriors accidentally traveled to his dimension instead of Hela's. However, that fell apart after he made a deal to allow Bor Búrison, AKA Bor's Valkyries, known as the Disir, stay in his realm. The devil later claimed that he put the idea of Cul's fear war into the Serpent's head. Also, during another of Blackheart's rebellious phases, Mephisto placed hell marks on the heroes who opposed him: Flash Thompson, AKA Agent Venom, General Thaddeus Ross, AKA Red Hulk, Laura Kinney, AKA X-23 (later Wolverine), and Alejandra, AKA Ghost Rider.
After the birth of the seven billionth Earthling, who happened to be Rahne Sinclar, AKA Wolfsbane's son Tier, the Hell-Lords set out to kill the boy. Mephisto's daughter Jezebel worked with X-Factor to stop this and even ran her father through with a sword. Upon realizing that Tier could kill them, Mephisto unleashed his power against his fellow Lords. During the confrontation he managed to capture the Hell-Lords. He also defeated most of the Earth's heroes and establish his own stronghold on Earth. However, Tier killed all of the captives. While Tier went after Mephisto, Guido Carosella, AKA Strong Guy–who had previously allied himself with Mephisto–snuck up and killed the boy, thus becoming the king of Hell. Mephisto regained his throne of power by working with Red Hulk's Thunderbolts, who convinced Strong Guy to abdicate.
During Hydra's Secret Empire campaign, their forces destroyed Las Vegas. The whole place was sent to Mephisto's realm afterwards. Not knowing about its new location, Doctor Strange attempted to restore Vegas to the land of the living. In doing so, he brought Mephisto, his Hotel Inferno, and a variety of demons with it. Though not a fan of living on the Earthly plane, the devil did appreciate how his casino could easily manipulate humans into handing over their souls.
Strange bet his soul that the devil would find good souls among the heroes. At that point, Mephisto possessed the Avengers, so another group came together led by Wong that also included Johnny Blaze, AKA Ghost Rider. They developed a plan that would find Mephisto lifting the Ghost Rider curse from Blaze before killing him. Johnny then managed to take over the throne of Hell, which led to Mephisto's imprisonment in the still-Earthly Hotel Inferno, but only after the hell-held Spirits of Vengeance were able to rough him up a bit.
Even though he was locked up and seemed to have dealings with King Blaze, Mephisto still had a variety of plots and schemes in motion, including the manipulation of Phil Coulson, the Squadron Supreme of Earth-712, Vlad Dracula, AKA Dracula, Namor McKenzie, AKA Namor the Sub-Mariner, Soviet super heroes and other players. Mephisto was killed by Marc Spector, AKA Moon Knight, in the Hotel Inferno. When Khonshu took over the planet, a variety of alternate reality Mephistos tried taking the moon god out, but were themselves killed. For a time after this he appeared only as a hellhound. Additionally, other demons seem to have taken Mephisto's form to confront other heroes.
Mephisto's Agent Coulson managed to find a Hellahedron or Pandemonium Cube, which he used to rewrite reality so that his lord was the major god and the Avengers never existed. Though the Squadron Supreme looked over the world, it still included a few Avengers who recalled their memories of what had been and fought to put reality right. Mephisto did not appear to help Coulson when the Avengers did exactly that. While addressing the Council of Red, Mephisto claimed that all of that was a way of showing what they could do if they truly worked together.
When Spider-Man faced off against Kindred, Doctor Strange once more bet his soul that Parker would prevail over the dark forces working against him, many of which were created by Harry Osborn before he died. The web-slinger persevered, which meant Strange won and thus Mephisto had to made good on their deal to release Harry Osborn's soul.
Unencumbered by space and time, the multiversal Masters of Evil began killing other universes and their Avengers. They even appeared in the present of Earth-616 to kill the Deathloks sent from the God Quarry, but Mephisto appeared to remind them that this reality was his. During this visit, he acquired the Watcher's eye from Doom Supreme who had killed the Orb. Shortly after, the devil pushed Serpent Solutions to lean back into its murderous days as the Serpent Society who were worshipping Mephisto. They were taken out by Kyle Richmond, AKA Nighthawk, created by Coulson. As the Avengers responded, they all encountered the devil and got their first look at the true power of the Council of Red. Though the full extent of Mephisto's plans remain a mystery, they will surely lead to some hard times for the Avengers and the world.