In biblical times, Cain made a deal with Lucifer to save his brother: Abel's soul in Heaven in exchange for Cain's soul in Hell. As part of the deal, Cain had to kill Abel himself and took on the Mark of Cain. Eventually, the guilt got too much for Cain and he killed himself with the First Blade, the weapon he had crafted to kill Abel. However, the Mark wouldn't let Cain go and transformed him into a very powerful demon and the first Knight of Hell. Following his transformation into a demon, Cain became the worst demon to ever live and was feared by all other demons. He gained many titles, one of which was the Father of Murder. Following the orders of Lucifer, Cain began to create an elite demonic order known as the Knights of Hell which were made up of demons hand-picked by Lucifer himself from amongst the very first demons to be created, making them very evil and very powerful. Under Cain's leadership and guidance, the Knights of Hell spread evil and chaos across the Earth for millennia before Cain suddenly vanished. Most of Hell believed he was dead, or at least hoped he was.
Unbeknownst to everyone else, Cain had fallen in love with a human woman named Colette Mullen some time before 1863. Colette knew who Cain truly was and what he was and accepted and loved him unconditionally. Her only request was that Cain give up his murderous ways and he did, suppressing the Mark of Cain's influence upon him and marrying Colette. However, the other Knights of Hell were not pleased by this development and became determined to get their leader back, particularly Abaddon who seemed to have romantic feelings for Cain.
Determined to get Cain back into the fold, the Knights of Hell kidnapped Colette to draw Cain out. Their plan backfired on them drastically as Colette's kidnapping drove Cain back to his old ways and he picked up the First Blade once more in order to rescue Colette and exact revenge upon the Knights of Hell. Cain began tracking down all of the Knights of Hell in his quest for Colette and slaughtered them all and any other demons that got in his way.
Finally, only Abaddon was left of the Knights of Hell and Cain tracked her to a cabin in Jasper Springs, Mississippi, some time after Colette's initial kidnapping. Reaching the cabin, Cain was faced with three demon guards who desperately tried to protect their master, but they were no match for Cain who easily killed them. Entering the back room of the cabin, Cain is excited to find Colette there, apparently unharmed, but quickly realizes that she's actually possessed by Abaddon. Cain demands to know what Abaddon has done to Colette, but she just asks him to make things right by returning to the Knights and to her. Cain refuses so Abaddon starts to snap all the bones in Colette's body to kill her in retribution, taunting Cain as she does so. Enraged, Cain tries to stab Abaddon with the First Blade, heedless of the fact that she is possessing his wife. However, Abaddon smokes out before Cain can reach her and Cain instead stabs and mortally wounds Colette. Cain desperately clutches the dying Colette, apologizing for his action and promising to track down Abaddon and kill her in revenge. However, Colette's last wish before dying is that Cain give up killing, even to avenge her, stating that there's been enough killing and he's better than it.
Following Colette's death, Cain chose to honor her last wish and buried Colette and walked away from a life of killing, even to the extent that he never went to get revenge on Abaddon. To get rid of temptation as the First Blade is indestructible, Cain throws it to the bottom of the Mariana Trench, the deepest part of the ocean.
Following the slaughter of the Knights of Hell, it somehow became widely believed that the archangels killed the Knights and not Cain. Cain himself stated that only he and Abaddon knew the truth, though Crowley learned it at some point as well. Cain retired and began living a life in rural Missouri as a bee keeper, developing an appreciation for bees. No one knew he was alive, though people searched for the First Blade as it was a powerful weapon to be wielded.
In early 2013, Abaddon resurfaced after disappearing for decades and being believed dead also following her massacre of the Men of Letters in 1958. Though defeated and imprisoned by Henry Winchester and his grandson Dean, Abaddon eventually escaped and began a crusade to take over Hell. To stop her, the King of Hell Crowley and Dean began searching for the First Blade, the only weapon that could kill her. Using a tracking spell, they found Cain who told them the story of Colette's kidnapping and reluctantly gave Dean the Mark of Cain and the location of the First Blade so that he could kill Abaddon. Breaking his promise to Colette, Cain slaughtered a massive army of demons sent by Abaddon after him and fell back under the influence of the Mark and returned to his old ways before being killed by Dean.