Deanna and Samuel Campbell were married hunters who raised their daughter, Mary, in the same lifestyle. Mary fell in love with a young John Winchester, who at the time knew nothing about the otherworldly creatures humanity shared the Earth with. The machinations of the demon Azazel led to the deaths of Deanna and Samuel, and Mary was forced to make a deal with the demon to save a dying John's life. It was this event that opened John's eyes to the truth.

A few years later, John and Mary married, and eventually had two sons named after Mary's parents: the elder, Dean, and the younger, Sam. In 1983, Azazel returns to fulfill his deal. Having secured Mary's permission to enter the house as part of the original deal, he sneaks into Sam's nursery and slits his own wrist, pouring demon blood down the infant's throat. Mary finds him and tries to save her son, losing her own life in the process. The house is set on fire as Azazel leaves, with John barely managing to get Dean and Sam out in time.

The death of his wife prompts John to immerse himself in hunter culture, fueled by the need for revenge. As Dean and Sam grow up, they find themselves frequently relocating all across the country, raised as hunters to help their father stop monsters and continue searching for Azazel. While Dean faithfully listens to his father's orders, Sam is more uncomfortable with it all, desiring to live his own life on his own terms. Another run-in with Azazel in New York City sets off a fight between Sam and John that ends with Sam leaving his father and brother, traveling across the country to live by himself. A couple of years later, he writes the LSAT and is admitted to Stanford Law.

Around 2005, John Winchester goes missing, and Dean travels to Stanford to ask Sam for help finding their father. Their search does not turn up any leads, and Sam returns to Stanford after telling Dean he does not want to be a hunter ever again. Once he gets back, however, he finds his girlfriend Jessica dead, pinned to the ceiling in much the same way Azazel killed Mary. Enraged, Sam agrees to join Dean to find their father, and ultimately Azazel.