When Sam Winchester was an infant and his brother Dean was four years old, their mother, Mary, was murdered on November 2, 1983 (All Souls' Day in the Roman Catholic Church). Her husband, John, saw blood dripping onto Sam's cradle, looked up, and found his wife pinned to the ceiling, her midsection sliced open. A moment later, she burst into flames. John told Dean to take baby Sam outside and made a desperate and futile attempt to save his wife while the house was consumed by flames.
After a psychic told John that a demon was responsible for Mary's death, he became obsessed with finding and destroying it. He trained his sons to recognize and defend themselves against paranormal entities. Sam and Dean became resourceful sleuths and experienced fighters as they assisted their father in his quest to destroy dangerous creatures and find the demon that had killed Mary. However, Sam chafed against the lifestyle his father chose for him, eventually falling out with his father and leaving to live a "normal" life. He attended Stanford University on a full scholarship and lived with his girlfriend, Jessica, in an apartment near campus. But when Dean appears one night during the autumn of his senior year, bearing the news that their father has gone missing while on a "hunting trip," Sam reluctantly agrees to help Dean look for their father.
The brothers trace John to Jericho, California, where they find more clues about their father's location and help solve a murder mystery. However, Sam declines his brother's invitation to continue the search and conduct more hunts, opting instead to return to his life with Jessica. Unfortunately, shortly after arriving in his apartment, he finds her pinned to the bedroom ceiling, bleeding from the abdomen. As Sam watches helplessly, she bursts into flames and dies in the same manner as his mother. Jessica was murdered exactly 22 years, to the day, after Mary. Dean rescues his brother from the burning apartment, and the bereaved Sam decides to resume the search for the demon who killed his mother and his girlfriend. The Winchester boys then pick up the trail of clues, while traveling the United States in their 1967 Chevy Impala, leading to the whereabouts of their missing father.
Eventually the brothers locate him, and he reveals the extent of his knowledge of the demon that killed Mary, and his intention to kill it. At first he opposes the boys' involvement because he fears losing them, but eventually he yields. The Winchesters now search for a special weapon: The Colt, which was created during the Alamo for a demon hunter, and has the ability to destroy any being with one bullet. All three Winchesters, after recovering the Colt from a band of vampires, band together and start to hunt the demon in earnest. However, due to a series of catastrophic events (beginning with John's capture), they are eventually overpowered by the demon, who, while possessing John, nearly tortures Dean to death before Sam can shoot him in the leg with the Colt. Sam tries to rush Dean and John to the hospital, but a demon strikes in the form of an oncoming semi truck, totaling the Impala and leaving all three Winchesters incapacitated. While in the hospital, John makes a deal to save a comatose Dean, trading the gun along with his own life. Both Dean and Sam struggle to cope with John's death while trying to continue their job.