- Jared Padalecki as Sam Winchester (23/23)
- Jensen Ackles as Dean Winchester (23/23)
- Misha Collins as Castiel (23/23)
- Felicia Day as Charlie Bradbury (21/23)
- Mark Sheppard as Crowley (18/23)
- Jim Beaver as Bobby Singer (6/23)
- Julian Richings as Death (4/23)
- Samantha Ferris as Ellen Harvelle (21/23)
- Alona Tal as Jo Harvelle (22/23)
- Nicki Aycox as Meg Masters (17/23)
- Adrianne Palicki as Jessica Moore (4/23)
- Anna Camp as Lucianna Gibbons (22/23)
- Bradley Whitford as God (19/23) and Timothy Huttle (3/23)
- Jesse Williams as Tate Donovan (22/23)
- Robert Sheehan as Henry Gillis (22/23)
- Matt Bomer as Scott Gillis (22/23)
- Dana Davis as Kimberley Avery-Simons (22/23)
- Magda Apanowicz as Helena Ore (22/23)
- Richard Ayoade as Campbell Stans (22/23)
- Rob Corddry as Kronos (18/23) and Isaac Gordons (2/23)
- Kevin Chapman as Poseidon (18/23) and Oscar Gordons (2/23)
- Isabel Lucas as Aphrodite (4/23) and Jeanine Whitmore (2/23)
- Rebecca Hall as Athena (5/23) and Katherine Heidelburg
- Joe Manganiello as Hephaestus (4/23) and Benjamin Goldstone (2/23)
- Chad Lindberg as Ash (3/23)
- Fredric Lane as Azazel (3/23)
- Mark Pellegrino as Lucifer (2/23)
- Jake Abel as Adam Milligan (2/23) and Michael (2/23)
- Cindy Sampson as Lisa Braeden (3/23)
- Rachel Miner as Meg (2/23)
- Rob Benedict as Chuck Shurley (4/23)
- Richard Speight Jr. as Gabriel (2/23)
- Emily Perkins as Becky Rosen (2/23)
- Osric Chau as Kevin Tran (3/23)
- Ted King as Hades (3/23)
- Shay Mitchell as Persephone (2/23)
- DJ Qualls as Garth Fitzgerald IV (2/23)
- Samantha Smith as Mary Winchester (2/23)
- Jeffrey Dean Morgan as John Winchester (2/23)
Following the defeat of Gadreel and release of Sam things go wonky in the world, those closet to the Winchesters lost in battle return: Ellen, Jo, Bobby and Kevin.
Castiel achieves a higher status of power and the titans of Greek legend surface from the depths of Tartarus as the Greek Pantheon returns, this time led by the dreaded titan Kronos.
The Big Man himself (God) comes down from his hidden sanctuary in Heaven to offer valuable insight for the Winchesters and the reformed gang.
Three rogue angel brothers part of a collective known as the Herectics plan on releasing their leaders from Heaven's most powerful prison.
Crowley re-emerges and finds himself at a struggle with the Greek god tyrants and nasty angels with his demon army dwindling.
Kronos seeks to personally eliminate the Winchesters and commit global genocide through releasing the dreaded Four Elementals: Earth, Air, Fire & Water.
The Herectic Brothers have a personal vendetta against Cass and The Winchesters, their guardian angel and the born-again Harvelles, Kevin Tran and Bobby Singer are instructed by God's command to assemble an army of special, young individuals who will serve as the Recruited Hunters for the coming war.
Master Hacker Charlie Bradbury returns to the scene along with the born again real Meg Masters who also join the fight.
1. The Thin Narrow Line: Written by Jeremy Carver Directed by Robert Singer
Summary: Dean abducts the new head Crossroads demon after Sam ends up in acoma and Charlie in critical condition following the battle with Gandreel and Metatron. Dean comes then to the Fates of Greek legend and is subjected to a trilogy of tests to save Charlie whilst Cass is charged with awakening Sam, by means of the most powerful, concentrated African Dream Root in creation. Following the trials miraculously Ellen and Jo, Bobby and the original Meg Masters are returned to life and delivered unto the Men of Letters base.
2. Hunter League: Written by Sera Gamble Directed by Guy Bee
Summary: Guided by the angel Joshua and Sam's delirious visions of the deceased Kevin Tran, The Winchesters & Miss Bradbury come to Battle Ground, Indiana and two young gifted hunters with connections to the Greek Pantheon. The Harvelles decide to take a trip to tie up "loose ends", Meg Masters goes to her parents and the site of her sisters' gravesite where she encounters local ghouls and Cass is abducted by a bandit of lost souls and becomes entrapped in the operating base of the reconstituted Greek Pantheon, led by the evil resurrected titan Kronos. Sam, Dean and Charlie in Battle Ground collaborate with the two hunters under Dean's orders as in a dream God tells they will serve to be a part of an army of hunters for the coming battle to end all battles, The five then begin on the case of three bizarre killings: A local stockbroker, lottery winner and secretary killed before a fourth intended victim: the town's local female mayor daughter who claims that one was killed by a dog, the other by a griffin and the secretary by a man who vanished into thin air. In exploring the case they find the culprit to be the Great Duke of Hell, Bune an ancient demon who by legend apparently possesses three heads, one of a dog, one of a griffin and one of a man. They find Bune is making crossroads esque deals with local down on luck mortals in Battle Ground whom in return for riches (granted by the deaths of resident rich citizens) infects them with demonic powers.
4. Death Unchained
19. Love Potion No. 9
21. The Air I Breathe
23. What If God Was One Of Us
- Jared Padalecki directs his first episode of Supernatural in Season 10
- The idea of Crowley being finally finished off by the Season's finale was constantly wrestled over as well as Crowley serving as the big bad for the season before Jeremy Carver and Robert Singer settled on bringing back the Greek Pantheon and crowning the titan Kronos the main antagonist for the Season's primary arc
- The first season to feature a central homosexual character who is male, potrayed by Jesse Williams who also portrayed a homosexual character in the Kevin Williamson drama The All
- Jeremy Carver and Sera Gamble on conceptualising the character of Lucianna Gibbons felt she wasn't significant enough as the lead recruit among the other young recruited main characters, so they threw in the storyline of her being the first cousin of Jessica Moore
- Rutger Hauer was originally considered for the role of Poseidon before the part went to Person of Interest actor Kevin Chapman
- The season marks the return of character Chuck Shurley who has been absent from the series since Season 5 and was a recurring character since the episode The Monster at the End of This Book, the season also marks the characters' final appearence
- The idea of the Elementals being a collective threat to the Winchesters and the other heroes in the season was inspired by the success and praise of their collective Four Horseman from Season 5