Preston Burke is the former chief cardiothoracic surgeon at Seattle Grace Hospital. He completed his pre-medical studies at Tulane University where he pledged Kappa Alpha Psi, and went on to graduate first in his class from Johns Hopkins School of Medicine. While in college, he met Erica Hahn, who graduated in second place after him, beginning a rivalry between them. He was once the interim chief of surgery while Dr. Richard Webber was healing from his brain surgery. In season 1 it is revealed that Richard had promised him the position but instead enticed his former student, renowned neurosurgeon Derek Shepherd, to Seattle as he felt Burke was becoming arrogant and needed competition to keep him on his toes. He began a relationship with intern Cristina Yang but broke it off because he feared it would ruin both of their reputations. Her miscarriage brought them back together. He and Cristina lived together in his perfectly kept apartment.
Towards the end of the second season, he was shot, which affected his control of his right-hand. His temporary fix to this possibly long-term problem was to work together with Cristina during every one of his surgeries so that she could take over in case he might have trouble with his hand. The arrangement fell apart after Cristina, reacting to growing stress after George O'Malley (T. R. Knight) caught onto their secret, went to the Chief and confessed everything. Initially, he was engaged in a cold war with Cristina, where neither of them spoke. However, after she broke the silence, he proposed to her and she accepted his proposal. Before their secret was revealed, Burke was to become the next Chief of Surgery, but he had to compete with his fellow attendings for the position. He has since recovered from the injury, after Derek operated on him. For the remainder of the season, Preston and Cristina prepared for the wedding and experienced normal stresses that result from such a process, such as meeting each other's parents.
However, in the finale of season three, on the day of their wedding, Burke told Cristina that he no longer wished to make her do anything against her will, and realized he was trying to make Cristina the woman he wanted her to be, and not accept her as the woman she is. Cristina said she "thought this was what she wanted." He wanted her to say she knew it was what she wanted, so he left her in the chapel. Cristina then returned to their apartment and discovered Burke had left, taking with him the things that meant something to only him (his trumpet, his Eugene Foote collection, his grandmother's picture, and his lucky scrub cap), leaving Cristina devastated.
In the fourth season, Preston's long-time rival and love-to-hate medic Dr. Erica Hahn replaced him as the head of cardiothoracic surgery. Before taking over the position she had tremendous respect for Burke although she would have never admitted it to his face. Hahn disliked Cristina Yang because of her relationships with Dr. Burke and Colin Marlow. During his employment at a new hospital, he is made the recipient of 2008's Harper Avery, a highly prestigious medical award. Cristina is later hurt that he did not mention her in his article, even though Cristina helped Burke with his recovery from an injury.
In season ten, Preston is seen to be living in Zürich, where he runs a privately owned cardiothoracic research hospital. He invited Cristina to the hospital to give a speech on her research. Cristina is both shocked and angered by the sight of Preston, and the former couple exchange bitter sentiments. Cristina claims that the two would never have worked out because she wanted to emulate him, not be by his side. Preston then reveals his ulterior motive for bringing Cristina to Switzerland: to ask her to take over his hospital, which she accepts. He is married to an Italian woman, Edra, and has two daughters, Simone and Vivianna. They are on the verge of moving to Milan.
