Callie Torres is introduced as an orthopedic surgeon with a crush on intern George O'Malley. The two start a relationship and Torres moves into Meredith's house (Meredith and Izzie Stevens lived there as well). Uneased at the way their relationship is progressing, O'Malley confronts her, which results in her moving into a hotel. In the aftermath of the breakup, she meets and has a one-night stand with plastic surgeon Mark Sloan, who becomes her friend. Torres and O'Malley subsequently reconcile, and the two marry in Las Vegas on the spur of the moment. Confused, O'Malley confides to fellow intern Izzie Stevens, about his relationship woes over alcohol, leading to a drunken sexual encounter between the two. Torres remains unaware of his sexual encounter, but becomes increasingly suspicious, and announces her desire to conceive a child. Shortly thereafter, however, she discovers that O'Malley has been unfaithful, ending their marriage. Though her personal life is troubled, Torres thrives professionally when she is appointed as the hospital's Chief Resident. However, she soon begins struggling to cope in the role, and is demoted soon thereafter.
Torres forms a friendship with Erica Hahn, the hospital's new chief of cardiothoracic surgery. The two embark on a relationship when Hahn jokingly kisses Torres in an elevator to tease Sloan. Neither has been with another woman before, and Torres struggles with her bisexuality, and cheats on her with Sloan. She is initially forgiven, but after an argument about work, Hahn resigns from Seattle Grace, ending their relationship. New pediatric surgeon Arizona Robbins kisses her, and they begin dating. Their relationship is tested when Torres comes out to her father, Carlos, who disowns her, cutting her off both financially and emotionally. When she is not granted a position as an attending, she publicly berates the chief, Richard Webber, and resigns from her post. She begins working at the neighboring Mercy West hospital, and when the two hospitals merge, she is promoted to an attending surgeon. Torres' father returns yet again, to condemn her, but ultimately accepts her sexuality. When Torres explains her desire to bear children, Robbins expresses disappointment, and their differing stances on the matter lead them to break up. Soon thereafter, a gunman commits mass murder at the hospital, and, relieved to have survived, Torres and Robbins reconcile, with Robbins agreeing that they should have children together.
When Robbins wins a prestigious grant to help treat children in Malawi, a disgruntled Torres agrees to move there with her, as the position will last for three years; however, her lack of enthusiasm causes Robbins to end their relationship and go without her. A heartbroken Torres moves in with Sloan, and they have a one-night stand. Robbins returns for Torres, apologizing and hoping for forgiveness, but Torres initially rebuffs her, and later reveals that she is pregnant with Sloan's baby. Robbins agrees to raise the child with her, but dislikes that Sloan will be a permanent part of their lives. En route a weekend getaway, Robbins proposes to Torres, but before Torres can reply, the two are in a head-on collision with a truck, leaving Torres severely injured. In an attempt to save her life, obstetrician-gynecologist Addison Montgomery, delivers Torres's premature baby. Torres survives, and agrees to marry Robbins. After twelve weeks of recovery, both Torres and baby Sofia are discharged and allowed to leave the hospital. Torres recovers from her surgery, but deals with the backlash from her mother's attitude toward the wedding and her granddaughter. Torres and Robbins marry in a garden after the minister's wife falls ill, with general surgeon Miranda Bailey, officiating the ceremony.
In the aftermath of a plane accident that killed Sloan and Lexie Grey, Torres is forced to make the decision to have Alex Karev amputate Robbins's left leg to keep her alive, which puts strains on their relationship. The hospital is sued and eventually found guilty of negligence. Each victim, including Robbins, Derek Shepherd, Meredith Grey, and Cristina Yang must receive $15 million of compensation, which leads the hospital to a near bankruptcy as the insurances refuse to pay. These doctors and Torres buy the hospital with the help of the Harper-Avery Foundation to prevent it from closing, and each become members of the new directing board. Everything seems to go well for Arizona and Callie, until a big storm hits the hospital now named after Mark Sloan and Lexie Grey. In the last episode of the ninth season, Arizona cheats on Callie with Dr. Lauren Boswell. Callie soon discovers Arizona's infidelity by seeing her wedding ring pinned to Dr. Boswell's scrub top. In the aftermath of discovery, both Callie and Arizona share their feelings and it is revealed that Arizona does not forgive Callie for making the call to amputate her leg. Callie is heartbroken and Arizona states that Callie lost nothing in the crash, to which Callie responds that she, apparently, lost Arizona.
Callie takes Sofia to live with Meredith and Derek, Zola, and Baby Bailey for a while before kicking Arizona out of their apartment and celebrates by dancing in her underwear. Callie also left Arizona at therapy, telling her that she was the only one that needed to go. After being hit by a lawsuit, her father, Carlos, visits and tells Callie that he cheated on her mother but she took him back and Callie wouldn't be here if her mother didn't give Carlos a second chance. Callie goes to Arizona's apartment and invites her to come back home. Callie finds out during surgery that Arizona was sleeping with Leah, a second year resident, while separated. Although angry at Arizona, Callie still agrees to work things out.
After April's failed wedding to Matthew, Callie and Arizona bought a house together, a fresh start, away from the memories of their apartment. They later decided to try again for a second child. However, a trip to the OB/GYN led to the discovery that Callie had developed adhesions in her uterus in the years since Sofia's birth, meaning she could not carry any more babies. After talking about it, the couple agreed to postpone their dream to have another baby until they're on more solid footing as a couple.
At the beginning of the eleventh series, Callie and Arizona gave therapy another chance in order to help mend their marriage. They were made to go 30 days living separate lives in the same house with no sexual activity with others or each other. They come close to breaking that rule and had to start over and before the 30 days was up they eventually gave in and connected sexually again. At the end of the 30 days at the final therapy session Arizona realized she couldn't live without Callie; however Callie didn't feel the same and stated she felt suffocated and eventually walked out of therapy, ending their marriage.
Callie then goes on to date Penny, who was the resident in charge of Derek Shepard's case. She comes to a dinner party hosted by Meredith, who recognizes her. It is then discovered that Penny is going to be working at Grey Sloan Memorial. When everyone, including Callie, finds out who Penny actually is, they protest and try to get her off of the Grey Sloan Memorial residency line. She manages to stay on the line despite all the other's pleads and wishes.
After Callie discloses her desire to move to New York with Penny and take her and Arizona's daughter, Sofia, with her, Arizona takes Callie to court for sole parental custody. Callie loses custody of her daughter to Arizona and Penny moves to New York. After Arizona decides that both Sofia's moms deserve to be happy, Arizona presents Callie with plane tickets and offers a custody agreement that keeps Sofia in Seattle for the summer and then sharing her every other school year and Christmas.
