Sam and Dean Winchester were trained by their father to hunt the creatures of the supernatural. Now, their father has mysteriously disappeared while hunting the demon that killed their mother, 22 years ago.
Sam and Dean are called in to investigate when a plane crashes under mysterious circumstances, leading them to the conclusion that a demon is possessing people and causing them to crash the plane they are on.
Following visionary Sam's recent nightmare about the former Winchester home in Lawrence, Kansas, where the present dwellers, Jenny from Wichita and daughter to two small kids, are suspiciously accident-prone, Dean reluctantly accepts to drive there. Dean and Sam reassure Jenny but follow up on the kids fear of a flaming creature in the closet. They consult Missouri Moseley, their father John's old medium friend, and together with the spirit of Mary Winchester, confront an evil poltergeist, but a second ghost intervenes and someone hides behind Missouri.
Sam and Dean investigate an abandoned sanitarium and discover that when the hospital was open, the patients held a revolt against the cruel and unusual experimental treatments carried out by the head doctor. Now the ghosts roam the halls, driving anyone who spends the night insane. While trying to rescue two lost teenagers, Sam is captured and turns against Dean.
While in a motel, Sam and Dean receive a call from their father, asking them to give up trying to find him and to take note of the names of three young couples that had disappeared in Indiana along the last three years, always on the second week of April. Sam decides to go after his father in California and leaves Dean, who arrives in the small town of Burkitsville for investigation of the missing couples. Sam meets the drifter Meg, who is also hitchhiking to California on the road, and stays with her waiting for a bus in the bus station. Dean discloses that a pagan ...
When Dean is accidentally electrocuted fighting a monster, he permanently damages his heart. When he's diagnosed as only having a month, at most, to live, Sam searches for a means to save him and finds Roy Le Grange, a faith healer who may actually be the real deal. After Le Grange heals Dean, the brothers discover that Le Grange is using black magic to bind a "Reaper" to do his bidding... and each healing comes with a terrible price of someone else's life.
Sam has a premonition in which a man is killed, but the murder is made to look like a suicide. Sam convinces Dean that they must investigate the case, but the two are puzzled when they fail to find anything that indicates that the death was supernatural in nature. That is, until they find out that Max, the reclusive son of the first victim, has been using his recently acquired power of telekinesis to kill the family members that once abused him. Sam also discovers Max's mother was killed by the same fiery demon that took his own mom.
Sam and Dean investigate the case of a maniacal ghost inhabiting a long abandoned Texas farmhouse known as "Hell House." They believe the ghost is the spirit of a deceased Depression-era farmer who killed his family.
Sam and Dean investigate a small town in Wisconsin where children are falling into comas for no apparent reason and discover that a witch is creeping into the bedrooms of the children and stealing their "life force."
A young couple is murdered in their home shortly after buying an antique painting of a family portrait circa 1910. Upon reviewing the painting's provenance, Sam and Dean learn that everyone who has ever bought the painting has been murdered and race to discover how the portrait is causing the deaths before it can claim its next victim.
After Daniel Elkins, a vampire hunter and John's mentor, is murdered, Sam and Dean are surprised when John himself shows up to solve the case. John discovers the vampires have taken an antique gun, which has the power to kill all supernatural beings. The Winchester family sets out to retrieve the gun from the vampires so they can use it to kill the demon that took Sam and Dean's mother.
Meg turns to killing John's friends in order to get the Colt. Sam and Dean stakeout the Demon's next target; a family with a six month old baby showing signs of special abilities. John heads off alone to confront Meg.