"Creatively, I really feel like I gave it my all, and I feel ready to let her go," an emotional Oh tells THR of her decision to exit at the end of season 10.

ABC's Grey's Anatomy is losing one of its original and most beloved stars.

Sandra Oh has opted to exit the medical drama from Shonda Rhimes, The Hollywood Reporter has learned exclusively.

Oh has played prickly doctor Cristina Yang since the series premiered in 2005 and will exit ABC's top-rated drama following the completion of its upcoming 10th season. The actress, who was among the stars who signed new two-year deals in May 2012 to return to Grey's through season 10, instead will pursue other opportunities beyond the series.

"Creatively, I really feel like I gave it my all, and I feel ready to let her go," an emotional Oh tells THR. "It's such an interesting thing to play a character for so long and to actually get the sense that she wants to be let go as well. [Cristina] wants to be let go, and I am ready to let her go. We have to start the process, story-wise, for the Grey's writers to think of why she's going to go."

PHOTOS: 'Grey's Anatomy's' Famous Departures

Oh says she first began thinking about wrapping her Grey's run in May 2012 when what she called the "original six" inked new two-year deals to take them through the 10th season of the series. "I've gone through a lot of therapy over this," she says through tears. "I started thinking about it because I had to prepare myself. I gave myself two years to emotionally let go. At the end of last season, Shonda took me aside and said, 'What are your thoughts?' I said, 'I'm ready.'"

Oh informed her co-stars about her upcoming exit during Tuesday's table read for the show's 200th episode and said the decision "doesn't feel real" yet. "I seriously think I need that much support over processing it over this next year for me to be able to leave fully and leave in a way that I feel like Cristina deserves," she says, noting that Rhimes has supported her every step of the way. "For the first time, at least for my character, you actually have an endpoint, which in series television you never or very rarely have."

Rhimes has repeatedly noted that she sees herself in Cristina's character -- a driven doctor who repeatedly puts her professional life first and foremost over her personal affairs. The character was the second one Rhimes created -- following Ellen Pompeo's Meredith Grey.

"One of the best days of my life as a writer happened the day Sandra Oh walked in my door to audition and forever changed the course of Grey's Anatomy with her brilliant, nuanced portrayal of Cristina Yang," series creator/showrunner Rhimes says. "Over the past 10 seasons, I have been made better by Sandra's trust, faith and friendship, and I can't quantify how grateful I am for her collaboration on a character we both love so deeply. This year is going to be bittersweet for us -- we're both going to savor every moment of Cristina Yang, and then we're going to give her the exit she deserves. And when Sandra walks out of my door, Grey's Anatomy will once again be forever changed."

It's unclear just how Oh's exit will be handled on-screen. No additional castmembers are expected to be departing at this time, though the two-year contracts for stars Patrick Dempsey (Derek), Pompeo (Meredith), Justin Chambers (Alex), James Pickens Jr. (Webber) and Chandra Wilson (Bailey) are up at the end of season 10. (Dempsey recently told THR that "it's worth having a discussion" on whether he would continue on at Grey's. "Whether or not we're in the show, I think the show will continue on," he said. "I know Shonda would like it to.")

"It's our intention to have Grey's on the air for many years to come, with as many of the original cast as possible," ABC said in a statement. Sources tell THR that negotiations will begin shortly with remaining original stars Dempsey, Pompeo, Chambers, Pickens and Wilson to continue on with the series after season 10. Oh's onscreen love interest Kevin McKidd will remain with the series beyond this season. "I want everybody for as long as they want to stay," Rhimes tells THR.

ABC Entertainment president Paul Lee hinted that there could be cast departures coming this season on Grey's Anatomy during his recent presentation at the Television Critics Association's summer press tour, noting that Rhimes was "planning a number of series out[s]." "We would like to see [Grey's] on the network for many years to come," he said.

Oh has earned five supporting actress Emmy nominations for the role, which originally was not envisioned to be an Asian-American. She is a four-time Image Award nominee, two-time People's Choice Award nominee and won the Golden Globe in 2006 for the part. In addition to a nomination for the Grey's ensemble, Oh also took home the SAG Award for actress in a drama series in 2006.

STORY: Emmys 2012: 'Grey's Anatomy's' Sandra Oh on Cristina's Emotional Season

During Oh's 10-season run, Cristina has been a vehicle for Rhimes and the Grey's writers to explore often controversial subject matter such as abortion and interracial marriage as well as PTSD -- three times -- including after a plane crash that claimed the lives of two former series regulars (Eric Dane, Chyler Leigh). As much as Grey's has been the story of Meredith and Derek's romance, it's as much about the former's relationship with her best friend Cristina and her on-again, off-again romance with Owen (McKidd).

"I want this to be a celebration," Oh says of Cristina's final run. "I want us to get to that point where we see this character ride off into the sunset. Letting go of such a huge part of my life … I want to cry right now. Grey's has been the most important role of my life. Playing Cristina and growing her and growing myself in her, I want to usher her into the next section of her life in the best way possible. It's got to be Cristina Yang's happily ever after."

During the season-nine finale, Cristina and Owen firmed up their split. Oh's character reaffirmed her desire to not have children -- a decision she has firmly maintained since Day 1 of the series -- and decided not to stand in the way of Owen finding happiness. "I feel like that was a very definite moment for them," Rhimes told reporters in May of the fact that Owen didn't run after Cristina despite professing his love for her. "Do they still love each other? Absolutely. Is that love ever going to die? I don't know. I know a lot of fans just want us to end everything by giving Cristina a baby [as if that's] going to make everyone happy, which infuriates me as a woman, as a human being and as someone who loves babies -- it drives me nuts. I adamantly stand by Cristina's ability and desire to not have a baby and to be happy about that. There's something great about this struggle and what's going to make her happy and see where they go next."

PHOTOS: The Couples of Shondaland: 'Grey's Anatomy,' 'Private Practice,' 'Scandal'

Oh cited McKidd -- whom she called the "greatest acting partner you could ever ask for" -- for creating a place where she didn't feel as if she were acting but instead what Stanislavski called a "state of being." "You're not acting, you are in a state of being and you actually are the character," she says. "To actually get to the point in my career where you can experience that was the highlight of my career. Learning the rare opportunity of what it is to work on one project for 10 years -- that's like being married in television years for like a thousand years."

Added McKidd of Oh's upcoming exit: "I feel so blessed and grateful to have been given the chance to work with her. When I joined the show in season five, she was so welcoming and nurturing to me as a new actor on the show -- something I will never forget and be always thankful for. Getting to act with her every day has made me a better actor, and getting to know her has made me a better person. She is an extremely warm and loving person and I will miss her. I wish her every good wish in the world and will miss her at work a huge amount, but I feel happy to know that she is moving on to new adventures and roles to explore. Sandra has inspired me to diligently work hard at my craft and to never phone it in or zone out -- her professionalism and passion for acting knows no bounds. I have been lucky to get the time I have with her."

Oh becomes the latest Grey's star to exit the drama. She joins Dane, Leigh and Kim Raver (Teddy), who was written out in the season-eight finale; original star T.R. Knight (George) exited in 2009; Isaiah Washington (Burke) was fired in 2007; and Katherine Heigl (Izzie) left in 2010 to pursue other opportunities.

PHOTOS: Broadcast TV's Returning Shows 2013-14

Kate Walsh's Addison character was spun off to star in Private Practice, which recently ended its six-season run. For her part, Rhimes has noted she'd like both Walsh and former Grey's recurring player Caterina Scorsone to return before Grey's ends its run.

And Oh would be game, too. "There's no way that no one could keep me away from that," she said of an appearance in Grey's Anatomy's eventual series finale -- provided Cristina survives.

In the meantime, there's still the 24 episodes of season 10 for Oh to get through before she focuses on saying a final goodbye to her co-stars and Grey Sloan Memorial Hospital.

"I'm just going to focus on every single day," she says, noting she'd likely keep Cristina's stethoscope and ID badges as keepsakes. "I just can't think about it right now."

Grey's ranks as ABC's No. 1 drama among the advertiser-coveted adults 18-49 demographic, finishing its ninth season with an average of a 4.1 rating. In total viewers among original scripted dramas, it trails only Castle at the network.

Grey's Anatomy, which was renewed in May for a 10th season, returns Sept. 26 with a two-hour premiere. The drama also recently promoted four recurring players to series regulars as the show looks to continue on with its latest class of interns, something Lee stressed Rhimes has done before on the series. "She will, like she always does, bring changes that are extraordinary," he said.

And while Oh eyes her next career endeavor -- likely a return to the theater -- one thing will be certain: The actress will keep up with her co-stars every Thursday at 9 p.m.

"I feel like in 10 or 20 years, when I'm lounging around in my muumuu with a martini, I'm going to watch Grey's Anatomy from the pilot to whenever it ends, and I'm going to enjoy myself thoroughly and enjoy seeing all those moments and being able to see it with a new perspective," she says, reflecting on what has been a career-defining role.

Stay tuned to THR's The Live Feed for more on Oh's Grey's Anatomy departure.

E-mail: Lesley.Goldberg@THR.com

Twitter: @Snoodit