Grey’s Anatomy is not just a long-running hit medical drama—it’s a pop culture reference point that thrives on breathtaking plot turns, gritty back-stage scandal, and fatalities that leave audiences buzzing for years to come. Some of them were bound to happen, and others caught us off guard, but all of them left an impression. So here are the 14 most dramatic cast farewells the series has ever seen—counting down, of course, because that’s only fitting in Shonda-land.
14. Ellen Pompeo (Meredith Grey)
The face and heart of the show, Ellen Pompeo, stepped down as a series regular after more than 400 episodes. She admitted she chose security and a massive paycheck over seeking out “perilous” acting roles, signing a deal for about $20 million a year. While she still pops up sporadically and remains an executive producer, Meredith’s reign at Grey Sloan is officially finished.
13. Justin Chambers (Alex Karev)
The viewers were left stunned when Alex Karev left after 16 years. The writers of the show showed him the door to Kansas, where he reunited with Izzie and their kids. Chambers had said that he wanted to expand his career and try out new characters outside the comfort of Grey’s. In his own words, he has been going after more complex, darker characters since then.
12. Jesse Williams (Jackson Avery)
Jackson’s exit in season 17 tugged at heartstrings. Jesse Williams felt it was a necessary turning point in the character’s arc and departed to search for new opportunities. Jackson’s move to Boston gave closure to his story, but Williams has returned for cameo roles to leave that door slightly ajar.
11. Giacomo Gianniotti (Andrew DeLuca)
DeLuca’s dramatic on-season 17 death—stabbed pursuing a human trafficker—was among the show’s greatest. Gianniotti shared he was grateful for how his character died and said it was a beautiful ending to DeLuca’s turbulent ride.
10. Sarah Drew & Jessica Capshaw (April Kepner & Arizona Robbins)
Season 14 featured viewers stunned by a double elimination. Sarah Drew and Jessica Capshaw were both written out in “creative direction,” stoking rumors that it had to do with Pompeo’s big new salary. April was in harmony at a clinic, and Arizona moved to New York to co-parent with Callie.
9. Eric Dane (Mark Sloan)
McSteamy’s tragic death in season 9 still hurts. Eric Dane originally departed to pursue other ventures, though afterwards admitted the decision wasn’t entirely his. Fans nonetheless got a sweet and poignant closure when Mark was reunited with Lexie in the afterlife after the plane crash storyline.
8. Chyler Leigh (Lexie Grey)
Lexie’s untimely death with Mark was another tearful moment. Leigh requested to leave to ground herself on her family, and Shonda Rhimes worked with her to get her to write a good goodbye. Leigh then went on to appear in Supergirl when she reprised for a dreamy cameo in season 17.
7. Patrick Dempsey (Derek Shepherd)
McDreamy’s season 11 death shook the fanbase. Offscreen, Dempsey said it was a natural progression, but behind-the-scenes gossip later reported tension with the cast and crew. His feud with Pompeo and Rhimes clearly sealed his fate. Even so, his dream sequence appearances gave fans one last dose of MerDer magic.
6. Sandra Oh (Cristina Yang)
Cristina’s departure in season 10 was a class in refined storytelling. Sandra Oh just felt it was time to go after having given the character her best. Cristina’s move to Zurich gave her a good send-off, and though fans still beg to have her back, Oh has emphatically declared that she’s closed the book.
5. Katherine Heigl (Izzie Stevens)
Heigl’s season 6 dramatic departure followed public criticism of the show’s writing and her removal from Emmy consideration. She later regretted how she was being interpreted. Izzie’s departure divided the fans, and Heigl’s career took a different turn afterward, with roles on Firefly Lane and otherwise.
4. T.R. Knight (George O’Malley)
George’s horrific death following his rescue of a stranger from a bus crash remains Grey’s darkest moment. Knight left after becoming upset with having no storylines and speaking with producers. Off-stage conflicts—like Isaiah Washington’s infamous slur—also weighed on his tenure.
3. Isaiah Washington (Preston Burke)
Burke’s season 3 departure was surrounded by off-screen scandal. Washington was fired after using a homophobic slur to refer to Knight, which resulted in a fight with Patrick Dempsey. On the show, Burke left Cristina standing at the altar—a mean scene. He did return for a season 10 cameo to help close out Cristina’s story.
2. Sara Ramirez (Callie Torres)
After season 12, Ramirez confirmed they were departing Grey’s to develop individually, stating they had reached “emotional and physical capacity” with the character. Callie’s departure to New York was the end of a trailblazing run for LGBTQ+ representation. Ramirez then came out as non-binary and has since caused a stir in shows like And Just Like That.
1. The Legacy of Grey’s Exits
Every one of their departures—hurt, sudden, or messy—has redefined Grey’s Anatomy in unforgettable ways. These exits have launched fan debate, fueled headlines, and reminded us that drama never ends at Grey Sloan, on or off the screen.
If there’s one constant in Grey’s Anatomy, it’s that nobody’s job is ever safe. But every goodbye, no matter how painful, has kept fans hooked for nearly two decades—and made sure the show stays just as unpredictable as day one.