Sam Spencer was raised by his older sister, Olivia, after their parents' death but rebelled and ended up being thrown out of various boarding schools. After being thrown out of another boarding school in late 2000, Sam came to Springfield to live with Olivia. Sam then enrolled in public school and met young runaway Susan Lemay whom he convinced to return home. Little did he know that her family would soon be connected to his because Susan's great-uncle was none other than Sam's future brother-in-law, Josh Lewis! It was through the Lewis clan that Sam would meet Josh's wild daughter Marah. Instantly attracted to Marah, it was obvious to him that she was attracted to bad boy, Tony Santos. Though he tried to show Marah that he was the right man for her, he was unsuccessful and began a friendship with Catalina, an immigrant who lived with Marah's mother. Not long after Sam roped Marah, Shayne, Tony, Susan and Catalina into a scheme to make and sell pirated CDs that got them arrested by the FBI! Luckily, when the band decided not to press charges, the teens were let off the hook. As his sister Olivia continued her up-and-down relationship with Josh, Sam continued to pine for Marah, constantly trying to keep her and Tony apart. Eventually, through circumstances that had nothing to do with him, Marah and Tony split in 2001. Marah then began dating Sam, but nothing serious happened. Though Tony and Marah reunited, they broke up again, with Marah again turning to Sam though she still loved Tony. Later, Tony secretly cleared Josh's name after Josh was implicated in white-collar crimes. However, Sam took the credit for Tony's actions, and when Marah learned that Tony was the hero instead of Sam she severed ties with Sam.

Afterwards, Sam took a job as cub reporter at the Springfield Journal, but while investigating the local mob, was hit in the back of the head by one of Carmen Santos's goons and somehow wound up with a deadly virus spreading around his heart. As he lay comatose, Claire Ramsey, Rick Bauer, and Mel Boudreau worked feverishly to find a cure, with Rick and Mel finally doing so. With a new lease on life, Sam decided to apply to Hunley College, a prestigious journalism school. To his surprise, he was rejected. After Olivia spoke to Alan Spaulding, Sam was accepted into the school (neither knew that Alan had secretly ordered the school to reject Sam in the first place). In March 2002. Sam said his goodbyes to Olivia with promises to call and write coming from both sides. His last stop before Hunley College was to see Marah. They managed to part on friendly terms, with Sam encouraging Marah to get back together with Tony.

A few months later, Sam returned briefly to visit Olivia. He found the listening devices that Alan had planted in her earrings and was last seen at her wedding to Alan. Sam briefly visited again in early 2003 after Olivia left him a phone message about her recent pregnancy. Sam's joy at being an uncle was dimmed when he learned she had slept with Phillip and Alan, wasn't sure who the father was, and was going about an elaborate plan to make sure Phillip was the father no matter what. Disgusted with her manipulations and what they would do to her baby's life, he walked out on her and went back to Hunley. In January 2004, Sam was on hand to take care of Olivia's secret--namely her baby, Emma, whom she had told everyone in Springfield had died. Willing to go along with Olivia's deception, since he knew she wanted to get her daughter away from the Spauldings, Sam took care of Emma while Olivia took care of things in Springfield. However, when Olivia learned that Phillip had a nervous breakdown while she was away, her plans changed and she ended up deciding to marry him. Although Olivia said she was doing this for Emma, Sam had reservations since he thought Emma should be in a home with parents who actually love each other. After being convinced that Olivia did truly care for and love Phillip, Sam agreed to go along with the plan and helped her get a hasty marriage to Phillip at Ravenwood Mental Hospital. Later, Sam found himself face to face with Phillip's daughter, Lizzie, who was the reason Olivia left Springfield in the first place. Wary of this teenaged girl who caused Olivia to fall when she was pregnant; Sam listened to Lizzie's claim that she wanted to make amends by talking to Olivia at Sam's. Not sure of Lizzie's motive, Sam tried to encourage Lizzie to meet Olivia somewhere else, however he did pass on her request to Olivia and mentioned that perhaps making peace with the Spauldings could be the right thing to do.

Sam returned to Springfield for an emergency visit in early 2008 when his recently discovered niece, Ava Peralta, urged him to come back home because Olivia was dying. Diagnosed with a weak heart months earlier, Olivia seemed to be at death's door. Luckily, by the time Sam got there, Olivia received a heart transplant. Unfortunately, it came at the expense of the man that Olivia grew to love: Olivia was given Gus Aitoro's heart after he died in an accident. Though Olivia was extremely depressed and guilty, Sam was happy that his sister got another chance at life. After saying hello to his friend, Susan (Daisy) Lemay, Sam left town again.