Sam is the youngest child and only daughter of Peggy and Eric Mitchell. Eric died when Sam was ten and she was subsequently on the receiving end of her older brothers', Phil and Grant's heavy-handed paternalism.
Fifteen-year-old Sam follows her brothers to Walford in July 1990, unhappy at home because she dislikes their mother's boyfriend, Kevin Masters. She becomes friends with Hattie Tavernier and dates Ricky Butcher. Sam's family disapproves of the relationship, so Ricky and Sam decide to elope to Gretna Green in 1991; they marry despite the Mitchells trying to stop the nuptials. Peggy admits defeat and attends their more formal blessing in Walford a month later.
Sam fails to earn schooling qualifications, but she gains attention because of her looks after winning the title of "Miss Queen Vic" at the local public house; she starts to believe she can have a career modelling, but when she attempts to get a portfolio done by a professional photographer, he persuades her to do a topless shoot and the photos are then published in a pornographic magazine. This causes problems in Ricky and Sam's relationship, which is already under strain as Ricky is unable to provide Sam with the luxurious lifestyle she desires. After just a year of marriage, Sam grows bored and begins lusting after a playboy named Clive whom she meets at a New Year's Eve party with her friend Mandy Salter. After having a brief affair, Sam thinks she has fallen in love with Clive, but he makes it clear that he is only interested in sex when he tries to coax her into having a threesome. Realising that her marriage with Ricky is over, Sam leaves her husband and Walford in 1993 to take a job as a holiday rep on a cruise ship.
Sam returns in 1995, after her brothers, on a boys holiday in Spain, catch her in bed with David Wicks, and force her to return. Sam had tried to build herself a career as a model, but it had not gone to plan and she had ended up working as a hostess in a bar. Back in Walford Sam tries to continue her fling with David and when this goes nowhere she tries to come between Ricky and his girlfriend, Bianca Jackson. Initially, Ricky thinks he still has feelings for Sam, but eventually realises he is better off with Bianca and tries to let Sam down gently. However Sam won't take no for an answer and purposefully kisses an innocent Ricky in front of Bianca, causing them to split. Despite this, Ricky will not reconsider getting back with Sam and opts to try to make amends with Bianca. Sam is forced to admit defeat. Soon after, she meets a Spanish man named Guillermo, who is holidaying in England. When he invites her to join him in Spain she leaps at the chance and leaves Walford again in March 1996.
In 1999, Sam decides that she wants to settle down in Walford once more. During this time she embarks on a stormy relationship with Beppe di Marco, but she takes things more seriously than he does. After he finishes the relationship, a heartbroken Sam looks for comfort elsewhere. She turns to local club owner and Phil's adversary Steve Owen for support, but he is only using her to make his girlfriend Mel Healy jealous – so a hurt Sam decides to leave Walford once again in 2000.
In 2002, Peggy catches Sam working in a lap-dancing club in Spain. Ashamed and penniless, Sam returns to Walford with her mother and has a brief relationship with Steve until the latter's death at the start of March 2002. She then proceeds to have numerous flings with her cousin Billy Mitchell and Phil's archenemies, Trevor Morgan and Dennis Rickman, respectively – as well briefly having a relationship with her ex-lovers Beppe and Ricky. All of whom soon turn out to be using her to varying degrees. One night, whilst working in the pub, Sam is nearly raped by Dave Roberts. Sam manages to fight Dave off and escape the pub. When she begins flirting with Dennis' illegitimate father, Den Watts, she is left humiliated after he sacks her from her job at his family's club.
Animosity between the Watts and Mitchell families escalates. Sam is left in charge of the Mitchell empire when her brother, Phil, goes on the run after escaping prison for an armed robbery — for which he has been set up for by Den. Sam persuades Billy to torch Phil's snooker club in an insurance scam, an act that results in Den's club burning down and his daughter Vicki nearly perishing in the fire. Dennis vows revenge and he is only warned off when his friend Andy Hunter, the local crime kingpin of Walford, begins a relationship with Sam. They soon marry in September 2004, despite Sam's crush Minty Peterson attempting to stop the wedding — he has fallen in love with Sam and knows that Andy is only using her to gain control of the Mitchell assets. Andy fools Sam into signing over control of Phil's house, and she is then conned out of all the Mitchell businesses by family lawyer Marcus Christie and Den. Marcus tells Sam that Phil wants her to sell everything and give the cash to him. She does so, selling her mother's public house, The Queen Victoria, for a vastly reduced price to Den. Marcus is lying, and once he has the Mitchells' money, he flees, leaving Sam with nothing. Andy, realising Sam is no use to him, throws her out of their house – leaving her penniless.
Whilst trying to move on from her marriage with Andy, with the couple clashing with each other on several occasions, Sam becomes determined to get revenge on Den; she teams up with his wife Chrissie Watts and their neighbour Zoe Slater, who, too, had become a victim of Den as a result of her relationship with Dennis, to carry out their vengeful plot against Den. On the night of Den's wedding anniversary to his late wife Angie, the three women confront him at The Queen Vic shortly after he closes up. At first Den taunts Sam and her unlikely conspirators over their weakness, but it soon turns out that Den's adoptive daughter Sharon was overhearing the whole conversation; Chrissie had planned for Sharon to return to Albert Square so that she can overhear Den admit to his misdeeds and disown him in response, thus ridding Den of the woman he devoted as his daughter – and henceforth exacting revenge upon Den for what he did. This works successfully, and Sam even congratulates Chrissie for getting payback on Den – telling her "You're quite a bitch, ain't ya!". However, shortly after Sharon leaves Walford, Den returns to The Queen Vic and the event takes an unexpected and violent turn: Den suddenly attacks Chrissie and Zoe hits him over the head with Pauline Fowler's iron doorstop in defence, all the while Sam watches in shock. This is thought to have killed him; however, when Zoe and Sam leave the room, Den grabs Chrissie's ankle and she responds by hitting him on the head a second time – finally killing him. In the moment where Chrissie kills Den, however, Sam witnesses this and she later grows appalled when Chrissie allows Zoe to believe that her blow killed Den. As Chrissie has possession of The Queen Vic following Den's death, Sam blackmails her – threatening to unveil Chrissie as Den's killer unless she gives her the pub.
On the day after Den's murder, to which the square is unaware about yet, Sam is surprised to learn that Andy has died on the same night; Andy was murdered by his mob rival Johnny Allen after attempting to con him out of £750,000. In the events of Andy's funeral, Sam smugly attends his will meeting; she meets up with his solicitor and expects to receive all his money and assets. She promises to let Pat keep her job at the bookies, but inadvertently insults her by offering her cleaning work at the house. Sam is confused, however, when she is told that Andy had created a new will and is later stunned when Andy leaves the house to Pat Evans and the bookies to Dennis – whilst giving his and Sam's money to a dog's trust. She is further horrified when he leaves her nothing but a wedding ring and states "so she can sell it, get her roots done and still be the dumbest blonde I ever knew." – much to Pat's amusement. As she struggles to move on from Andy and their turbulent marriage, with Minty and his friend Danny Moon comforting her over the situation, Sam learns that Chrissie is attempting to sell the pub and leave Walford. She soon begins drinking heavily and, determined to expose Chrissie as Den's killer, smashes up Den's grave and digs him up.
Unfortunately for her, the plan backfires; all evidence points to Sam, who is charged with murder and remanded in custody. When Peggy returns to the square and learns about Sam's recent troubles, she visits her and Sam tells Peggy that Chrissie killed Den. Upon believing Sam, an outraged Peggy later confronts Chrissie at Den's funeral and smacks her onto his coffin – vowing to prove Sam's innocence. In attempting to secure Sam's release and expose Chrissie as Den's killer, Peggy starts a feud with Chrissie and later forms a conflict with Johnny when he and Chrissie build a partnership; with Peggy also resenting Johnny for the way how she treated her late husband and Sam's father Eric. Just as it appears that Peggy is unable to find a way of proving Sam's innocence, Phil and Grant return to Walford to secure her release. Eventually, with help from Sharon and Dennis – who end up learning the truth about their father's murder – the Mitchells are finally able to prevent Johnny from destroying the videotape of Chrissie confessing Den's murder to her boyfriend, Danny's brother Jake Moon; the police are given the tape and they end up arresting Chrissie at the airport for Den's murder. Sam is later released from custody; however, she still faces a charge of perverting the course of justice and faces a prison sentence up to four years. This prospect is too daunting for Sam, and she flees to Brazil while on bail in 2005.
In 2009, Phil sends Ricky to Brazil on an errand where he meets Sam, and she returns to London using a fake passport. She immediately causes a stir by drawing attention to herself and reignites her feud with Bianca. The Mitchells try to keep her hidden, but Bianca, jealous of Ricky's renewed feelings for Sam, calls the police. Sam is arrested while trying to flee but is released on bail when Ronnie Mitchell pays the surety. Sam and Ricky get engaged, but Sam has an affair with Jack Branning. Peggy's estranged husband, Archie Mitchell, uses Sam as a pawn in his plan to destroy the Mitchells, persuading her to jump bail again and leave the country to escape a prison sentence, so Archie can successfully steal The Queen Vic from Peggy. Sam opts to stay so Archie tells Bianca about Sam and Jack's affair; she tells Ricky and after a showdown, Ricky ends the engagement. Following this, Sam takes Archie's money and flees, causing the Mitchells to lose the pub. She returns to Walford on Christmas Day 2009, hoping to make amends. On that same day, Archie is murdered and Sam becomes one of the suspects. Phil, Peggy and Ronnie also have motives, and in order to stop the police framing them, they decide Sam should take the blame and leave the country. Sam overhears their plan and furious, turns herself in, implicating Peggy in Archie's murder for revenge. Sam is arrested and sentenced to 18 months in prison. When Peggy attempts to visit, Sam is hostile, rejecting her mother and disowning the Mitchell name.
Later in 2010, Peggy visits Sam in prison and discovers she is heavily pregnant. Sam does not know if Ricky or Jack is the father and she refuses to reconcile with Peggy; however when she is hospitalised and goes into labour, she reconsiders, requesting Peggy's help. Sam gives birth to a boy, Richard, but announces she is giving him up for adoption. She only reconsiders as a means to reconcile with Ricky; she returns to Walford having completed her prison sentence, but struggles as a parent and relies heavily on Peggy and Minty. Ricky and Jack pester Sam to a get a paternity test, which she eventually does. She lies, claiming Ricky is the father, however Bianca discovers the truth and Sam confesses that she has lied because Ronnie, Jack's girlfriend, asked her to. Ronnie does not want Sam or her baby near Jack. She manipulates Sam into leaving and pays her money to do so. Sam leaves but, fearful of bringing up her baby alone, she seduces Minty, who still loves her, suggesting he goes with her. Minty momentarily accepts, but then realises Sam is merely using him and turns her down. Sam departs with Richard, moving to Portugal to live with Grant.
Almost six years later, Sam returns to Walford alongside Richard, now nicknamed Ricky, in June 2016, to attend Peggy's funeral. She reveals that Grant is not attending and winds up Sharon about Grant, causing Sharon to reveal that she and Grant had kissed. Jack decides that he wants to see Ricky so Sam drops him at the Brannings. After the funeral, Sam gets drunk and Phil harshly confronts her causing her to leave the pub. Sam reveals to her cousin Roxy Mitchell that she is struggling to look after Ricky and that he is better off with Jack. Sam abandons Ricky at Jack's house and leaves in the back of a taxi.