Sam Winchester (Jared Padalecki) is a professional hunter of the supernatural. He travels across America with his brother Dean (Jensen Ackles), saving people from malevolent spirits, demons, and other entities. Although Sam was initially angry at his father John (Jeffrey Dean Morgan) for raising him in this strange life, he soon becomes more enthusiastic and ruthless while hunting. Sam also possesses some strong demonic powers that make him a target for supernatural and human enemies.
When Sam was an infant, his mother Mary (Samantha Smith) was found dead on the ceiling over his crib. She then burst into flames, destroying not only his home but all evidence of the strange crime. John, the only witness, was driven to seek out the supernatural world. He began to train his sons to fight supernatural evil, all the while searching for the demon that killed his wife. Sam disliked this transient and bizarre lifestyle and sought a normal life. He left his father and brother to attend Stanford University. While there, he fell in love with Jessica (Adrianne Palicki), a pretty student.
A few years later, Dean came to Sam for help as John had disappeared. Sam agreed to look for a few days, but the search was fruitless. Worse, when Sam returned home, he found Jessica dead in the same way his mother had died. He and Dean went back on the road, intending to find their father and defeat Jessica's murderer. Sam soon began showing signs of psychic powers; he would have visions and on one occasion displayed telepathy. The boys soon found John, but the reunion was short-lived. A yellow-eyed demon, Azazel (Frederic Lehne, various others), the same demon that killed Jessica and their mother, found them and seriously injured Dean. John sold his soul to Azazel to save Dean's life, dying in the process. However, before leaving, the demon revealed that he had plans for Sam.
Though still reeling from their father's death, Sam and Dean continued to hunt. They soon found more psychics like Sam; some seemed normal while others abused their powers. Eventually, these people were brought to an isolated area. Azazel encouraged them to fight to the death, claiming that the winner was destined to open a Devil's Gate and lead hell's armies. Though Sam and many of the others tried to work together to find a way out, one of them cracked under the demon's pressure and Sam was stabbed and killed.
Dean, devastated, decided he could not live without his brother. Following his father's example, he sold his soul to a crossroads demon to resurrect Sam. Dean was told the demon would come for his soul in one year. After Sam was resurrected, he and Dean managed to close the Devil's Gate and kill Azazel.
Sam soon found he could not help Dean cancel his contract. In his desperation, he turned to Ruby (Katie Cassidy), a demon who said she could save Dean's life. Though these claims rang false, she and Sam developed a close relationship. She encouraged Sam to embrace his powers, something Dean objected to. However, after Dean died, she helped pull Sam out of depression and taught him to use his powers to smite demons.
Dean was soon resurrected by angels who believed he could stop a coming apocalypse. Sam was overjoyed, but the reunion was soured when Dean learned that Sam nurtured his demonic powers. The brothers grew apart as Dean turned to the angels and Sam turned to Ruby (Genevieve Cortese). It was soon revealed that Sam often drank Ruby's blood in an attempt to strengthen his own powers. Sam became obsessed with killing Lilith (Rachel Pattee), a demon who tortured Dean. However, after he killed her, he learned that Ruby was in league with her, and that Lilith's death was a key component in releasing the devil from hell. It soon became clear that Sam had unleashed Lucifer on the world.
Sam then learned that he was Lucifer's vessel; his body was meant to hold Lucifer's consciousness. Dean, likewise, was meant to be the vessel for the archangel Michael. The two were destined to battle, which could lead to the destruction of the world. Sam and Dean reunited to prevent this from occurring. Eventually, Sam found a way to seal himself into hell with Lucifer, which returned the world to order. He made Dean promise not to go after him.
Sam changed significantly over the course of the show. Much of this is a result of embracing his demonic powers, but it is also due to increasing cynicism and an increasing belief that God no longer cares about the world. However, Sam managed to retain a close relationship with Dean despite their difference of opinion. Dean commented that their relationship was somewhat destructive, as many demons had easily exploited it to carry out their plans.
"We got work to do."
"You were gone. I was here. I had to keep on fighting without you. And what I'm doing, it works."
"I'm sorry, I am, but life doesn't turn out the way you thought it would when you were 14 years old."