Lexie is the daughter of Thatcher Grey and his wife, Susan. She has a younger sister, Molly Grey Thompson and an older half-sister, Meredith Grey who was born to Thatcher and his first wife, Ellis Grey. She was popular in high school, had a great group of friends, was crowned prom queen, and, later, was voted class valedictorian. Lexie has a photographic memory, which was highlighted in the fifth season when she remembered an illness she came across while reading medical journals for George O’Malley’s review. She could not only remember the diagnosis but the name, volume and page number of the medical journal earning her the nickname ‘Lexipedia’ by Alex Karev and Cristina Yang.
Lexie was more outspoken with the residents than the other interns, possibly due to the relationship with Meredith. She objected when Cristina Yang had the interns line up in the cafeteria to discuss which she would pass on to George (who had recently become a resident) disgusted they were being treated like ‘livestock’. When Alex Karev took over the several cadavers, used for surgical practice, Lexie had gathered for her fellow interns to use, she objects on behalf of the whole. However, she is seen to eventually acquiesce to her residents’ orders.
Lexie was assigned to surgical resident Cristina Yang for her year-long medical internship, and bore striking similarities to her half-sister, Meredith Grey. Initially, upon her arrival, Meredith wants nothing to do with her and is jealous of the life Lexie lived, feeling it was the one she would have had if her father stayed with her mother. Eventually, Meredith sits down with Lexie and explains the circumstances around her mother’s death while Meredith was caring for her (Susan having died in the previous season) and slowly they begin a friendship.
She forges a relationship with George O’Malley after becoming aware he is repeating his intern year, and they bond over their strained relationships with Meredith and Callie, respectively. She also begins a casual-sexual relationship with Alex Karev, reminiscent of the one between Meredith and Derek Shepherd. Meredith and Lexie grow closer when a patient Lexie has bonded with dies in her care and she is left devastated. By the end of season four, she begins to develop feelings for George O’Malley.
During the fifth season, her friendship with George slowly dissolves when he seemingly loses interest in their friendship after he passes his intern exam. Mark Sloan notices the tension between them and they begin an unsteady friendship, they are seen frequently bantering back-and-forth throughout the hospital. Both Meredith and Derek do not like the idea of Mark getting involved with Lexie, especially considering his reputation. Soon they begin a relationship causing another break in Mark and Derek’s relationship, to the point of a physical altercation, this causes Lexie to compulsively overeat, until the two reconcile their fractured friendship. In the season finale, Mark asks Lexie to move in with him but she refuses believing it is not a good time to move in together. Mark decides to buy a house for himself anyway, in attempt to get Lexie to believe he is moving on.
Season six marks Lexie’s first year as a surgical resident and one of the only two interns of her year saved from the Seattle Grace Mercy West merger. She also agrees to move in with Mark after a reassuring conversation with Callie.
When Lexie brings in her father, Thatcher Grey she learns his liver has been damaged by his alcoholism and he needs a transplant. Since he has not been sober long, he cannot be put on the transplant list, so Lexie gets herself tested. Mark is upset she didn’t discuss this with him, especially considering she is thinking of donating part of her liver to her alcoholic father. Unfortunately, Lexie is not a match, but discovers Meredith is, and begs her to do the transplant. Meredith agrees but makes it clear to Thatcher that she is doing it for Lexie, not him. Mark and Lexie make up after he is reminded ‘you always have to be there for people you love, even if they do things that don’t make sense.’
When Mark’s eighteen year old daughter, Sloan Riley arrives this causes tension between Lexie and Mark. After a paternity test confirms Sloan is actually Mark’s child, he becomes very fatherly and blind to his daughters selfishness. Sloan reveals she is pregnant when Lexie pressures Mark into asking Sloan how long she plans to stay in Seattle, especially since she is living in Mark and Lexie’s apartment. Mark assures Sloan she can stay for as long as she needs before and after the baby is born, stating both he and Lexie will help her raise it. Later, Lexie and Mark argue over his unilateral decision to ask her to stay and after Mark asks Lexie not make him choose between her and Sloan, because her will choose his daughter, Lexie kisses him and leaves.
Lexie moves back in with Meredith and Derek, she drunkenly sleeps with Alex Karev. When Mark returns from Los Angeles, he reveals to Lexie that he slept with Addison, and she, somewhat relieved, confesses her wrongdoing only to be rejected by him. Lexie and Alex resume their sexual relationship and it slowly blossoms into a full-fledged relationship. Lexie continually tries to prove she is over Mark but is reduced to tears when she finds out he took the new cardiothorasic surgeon, Teddy Altman out for dinner.
When Alex is shot in the finale, Lexie and Mark work to keep him alive and she confesses her love for Alex with Mark looking on, but it is unclear whether she really loves him or if she says it to keep him holding on till help arrives.
During the premiere of the seventh season Lexie is seen to be the most visibly affected by the shooting. It is revealed through a flashback she suffered a nervous breakdown while on duty at the clinic. Mark had to forcefully commit Lexie into psych to get her checked. Her nervous breakdown was caused by insomnia so she was sedated and slept for 50 hours straight. A week later, she was cleared for surgery.
Alex and Lexie are no longer dating, a fact which Lexie seems angry with him for his ungratefulness for her saving his life. She and Mark get back together but break-up when Callie reveals she is pregnant with Mark’s baby, one conceived from a drunken night in the on-call room. She begins a relationship with Jackson Avery which continues until the end of the season. In the season finale, she tells Mark she loves him but she cannot be with him because he doesn’t make her happy.
In her last season, Lexie is still dating Jackson and they both seem happy. When he realizes Lexie still has feelings for Mark he walks away from the relationship. She pines for Mark but focuses on her surgical career under the tutelage of Derek Shepard, she, like her half-sister, shows a talent for neurosurgery.
Near the end of the season, she confesses her love for Mark on the advice of Derek but Mark does not respond. There somewhat friendly relationship becomes intensely awkward up until the plane crash at the end of ‘Migration’. In the season finale, entitled ‘Flight’, Derek, Cristina, Arizona, Mark, Meredith, Lexie and the pilot are all struggling for their lives to varying degrees. However, none is in as bad shape as Lexie, who is crushed under a piece of the plane. Cristina and Mark try to move the piece off of her, but Cristina and Lexie both realize she cannot be saved due to the extensive injuries, including a massive hemothorax, caused by her being pinned under the debris.
Eventually, Mark comes to the realization Lexie is going to die and take her by the hand, telling her he loves her and he has always loved her and will always love her. As Mark tells her of the life the two were meant to have together, Lexie succumbs to her injuries and dies with a smile on her face just as Meredith and Cristina reach her.