The Gamble Era covers Season 6 and Season 7, when Sera Gamble took over showrunner duties with Robert Singer following the departure of Eric Kripke. The two seasons introduce loosely-related arcs as opposed to the Kripke Era, but both deal with the power vacuum left by the averted Apocalypse, and the collective rise of monsters to prominence. The former season begins a year from the aftermath of the Apocalypse, but also explains what happened in the interim. It features a three-way power struggle between Heaven, Hell, and a new major supernatural dimension, Purgatory. The latter introduces a drastic change in the balance of power as Castiel declares himself the new God, and with the arrival of new powerful beings referred to as the Old Ones from Purgatory.
|“||We thought season five would be the last season. But pretty early into [it], Eric came to me and said "signs are pointing toward a season six," and he was ready to move on and asked me to step in. And he came to me really early because there was a tremendous amount of learning and training and coming behind the curtain to see what he and Bob were doing that had to happen. There was part of me that was just, lovingly, super pissed at Eric. I was like, "do we have to do this after the apocalypse? We literally burned the story all the way to the apocalypse. We have to start over and find a whole new classification of villains, so what the hell are we going to do?" But we had several months to ponder that. We had a great writers' room, and everybody put their heads together, and Eric, to his great credit, stayed with the show, and was very active in constructing season six, and was incredibly helpful to me, personally. He was instrumental in figuring out what we were going to do next. It was like a reboot.||”|
— Sera Gamble 
|“||I didn't love [season six's] storyline as much as I loved some others, to tell you the truth. I thought we got off the ground really well. It was a provocative opening. I think that change in Sam's character were really interesting. But as the season went on, I thought the Campbell story wasn't a season's worth of work for me.||”|
— Robert Singer 
Heaven and Hell are both embroiled in civil wars of their own. Belligerents of Heaven are the archangel, Raphael, who wants to free his elder brothers to restart the Apocalypse, and the Seraph Castiel, who wants to retain the status quo and promote free will. The demons of Hell are split between its new King, then only King-of-Crossroads, Crowley, and the daughter of Azazel, who led the Lucifer loyalists.
The season also focused on souls, and was a major plot device for Sam Winchester's return from Lucifer's Cage, and for the struggles of the three supernatural planes. Eve, matriarch of Purgatory was drawn into the war and amassed an army of her own to prevent Crowley and Castiel from taking the souls in Purgatory to win their respective civil wars. The stand-off resulted in the death of Eve, and with Castiel betraying Crowley, the angel denying the demon of half the souls of Purgatory. Castiel killed Raphael and declared himself as the new God.
This season provides more depth to Purgatory lore as it introduces its oldest natives, referenced in the previous season as the Old Ones; the Leviathan. The Leviathan were God's first creations, predating angels, human and the soul. They are indestructible, intelligent, cunning, and were locked up in Purgatory for such reasons. They were absorbed by Castiel from Purgatory. The Leviathan soon overpowered Castiel and escaped his vessel. They took control of much of the economy and plotted to harvest humans as cattle, and at the same time, planned to eliminate competition from other beings, such as other monsters, and even demons. The Leviathans managed to bring the Winchesters on the run, and successfully killed Bobby Singer. The season ended with the Leviathan threat neutralized by the death of leader Dick Roman, and Dean and Castiel transported to Purgatory, Crowley taking captive of Meg, and the newly ascended prophet Kevin Tran, leaving Sam Winchester by himself.
The events of this era set up The Singer & Carver Era.