Crowley tells Bobby he will give him the location of Death, the fourth horseman, in exchange for his soul. Knowing Sam and Dean need that fourth ring to stop the Apocalypse, Bobby reluctantly agrees. Sam and Dean confront Pestilence, but he unleashes a deadly virus upon them, so Castiel must intervene on their behalf. Dean has a meeting with Death to discuss Lucifer, and an unholy alliance is formed at a very high price for Dean.
The demon Crowley tells Sam and Dean he can help them find the remaining Horsemen rings so they can trap Lucifer. The brothers are doubtful until Crowley leads them to Brady, the Handler for Pestilence and Death. However, Brady refuses to give up their locations and sets Pestilence after the Winchesters.
Sam and Dean are kidnapped by a group of gods, including Kali, Ganesh, and Baldur and held hostage in a small hotel. The gods want to use Sam and Dean as bargaining chips to stop the Apocalypse, but Gabriel shows up and warns them that if Lucifer finds them he will kill them all. Unfortunately, one of the gods turns on the rest and Lucifer appears.
Sam and Dean are outnumbered by demons, but are saved at the last minute by Rob and his townspeople, who are aware of the Apocalypse, and have been training to fight and kill demons. The small town is very religious and Sam and Dean meet Pastor Gideon, who introduces them to his daughter Leah, whom he claims is a prophet. Leah tells the townspeople they must obey her orders if they want a spot in Heaven but when she starts turning the townspeople against each other in the name of the Lord, the brothers realize they must kill her.
Sam and Dean investigate Bobby's home town where the dead are rising from the grave but instead of attacking humans, they are happily reuniting with their families. The brothers turn to Bobby for help but he tells them not to worry about it and to leave town. Suspicious, Dean investigates and comes face to face with Bobby's dead wife, who has no memory of what happened to her. Once the zombies start turning evil, the boys tell Bobby he has to kill his wife but he refuses.
The angels send Anna back in time to kill John and Mary Winchester before they can conceive Sam knowing that if Sam was never born then Lucifer won't be able to use him as his vessel. Castiel sends Sam and Dean back to 1978 so they can stop Anna, and the two brothers are reunited with their parents. Mary recognizes Dean as a hunter since he visited her in the past once before but tries to keep the truth from John.
Gary, a teenage nerd, conjures up a body-switching spell and changes bodies with Sam. Thrilled by his new handsome and built body, Gary (now Sam) investigates a case with Dean and takes advantage of his good looks and age by hitting on women and getting drunk. Meanwhile, Sam is stuck in Gary's teenage body, dealing with intrusive parents and high school.
A former hunter named Martin, who is currently institutionalized, calls Sam and Dean for help investigating a case in the mental hospital. The brothers get themselves admitted as patients to check out the mysterious monster that is attacking the patients, but their incarceration pushes both to the breaking point as they unleash their inner demons against each other.
When Sam and Dean find themselves living their lives on what appear to be TV shows, it makes for a whole new style of reality television and they wonder if the Trickster is to blame. From a sitcom to a soapy hospital drama to a Japanese game show to a crime procedural, each new experience they encounter is more bizarre than the next and they want out. But is the Trickster really the mastermind behind the madness?
Sam and Dean discover a witch is running a high-stakes poker game where the currency is life years vs. money. Bobby sees the game as a chance to get out of the wheelchair and bets 25 years, but loses. As Bobby begins to age rapidly, Dean steps in to save him but also ends up turning into an old man, leaving Sam holding the bag for their survival.
Sam and Dean investigate a series of odd murders that strangely resemble fairytales and urban legends. The brothers track down an 11-year-old boy named Jesse and realize that whatever Jesse believes is coming true. Castiel tells Sam and Dean that Jesse is a serious threat and needs to be eliminated.