Grey's Anatomy, spanning 21 seasons and 448 episodes, is one of the most popular medical dramas of all time. The show explores the lives of the medical professionals working in Grey Sloan Memorial Hospital, originally named Seattle Grace Hospital. Grey's Anatomy boasts emotionally driven narratives and intriguing character development that have kept fans invested for two decades.
This series, developed by Shonda Rhimes, has also become infamous for shocking character exits among viewers. While some succumbed to life-threatening injuries and diseases, others were written off the show as part of plot progressions that felt uncharacteristic and rushed. Irrespective of the reason, these exits not only impact fans but also other characters still in the show.
Out of all the characters exits in Grey's Anatomy to date, the ones mentioned on this list, like George O'Malley, Christina Yang, and Derek Shepherd, among others, left viewers particularly saddened and disappointed.
Disclaimer: This list contains information from various sources and has spoilers.
George O'Malley and six other characters' exits in Grey's Anatomy that left fans upset and shocked
1) Denny Duquette: season 2, episode 27

Given that Grey's Anatomy deals with medical emergencies, viewers are used to patients taking a turn for the worse. However, there are times when patient deaths hit hard, and this is exactly the case with Jeffrey Dean Morgan's character in season two, Denny Duquette.
Fans of Grey's Anatomy became invested in Denny's story because he was hospitalised for a long duration for his heart condition. During that time, he formed a romantic bond with Katherine Heigl's Izzie Stevens. In fact, Izzie became so attached to him that she risked her career to help him get on top of the transplant list.
Viewers were hopeful after he got a new heart that the lovebirds would be able to live out their happily ever after, but it wasn't meant to be. Soon after the operation, Denny died from a stroke. The death left fans in shock and impacted Izzie greatly as she had to deal not only with the trauma of losing him but also with the repercussions of her decision.
2) George O'Malley: season 6, episode 1

Grey's Anatomy viewers were used to saying goodbye to endearing patient characters who couldn't be saved. However, no one could have expected the writers of the show to make a main character face a similar fate.
When T. R. Knight's George O'Malley was rushed to the hospital, no one, including the audience and the other characters on the show, had any idea who they were treating because he was severely disfigured. As per their knowledge, John Doe had jumped in front of a bus to save a woman’s life. The realization dawned only when he traced "007" on Meredith’s (Ellen Pompeo) hand.
Even though they tried their best to save George, his brain swelled during surgery, and he was declared brain-dead. This was the first time that Grey's Anatomy fans witnessed the death of a main character, and were left shocked. As he was one of the original interns, the others were deeply affected by his demise.
3) Reed Adamson: season 6, episode 23

Aside from the main characters, Grey's Anatomy introduces a plethora of interesting recurring characters who add to the overarching narrative. Portrayed by Nora Zehetner, Reed Adamson was introduced in season six and had an abrasive personality, which meant that viewers didn't find her likable from the get-go.
But after spending time with the other residents, nurses, and interns, the Grey's Anatomy character seemed to be softening up a bit. However, viewers never got to see Reed evolve as she was shot right in the head by Michael O'Neill's Gary Clark, who went on a shooting spree after the death of his wife.
Clark also shot Alex Karev (Justin Chambers) and Charles Percy (Robert Baker). While Alex managed to survive, Charles died in Dr. Bailey's (Chandra Wilson) arms as she couldn't manage to get him to the operating room in time. Both deaths left the audience in shock at the suffering and helplessness that shooting victims experience.
4) Lexie Grey: season 8, episode 24

Even though fans of Grey's Anatomy were introduced to Chyler Leigh's Lexie only in season three, her vulnerable yet witty demeanor managed to win them over almost immediately. Initially, Lexie's story arc was meant to last a couple of episodes, but the character's popularity encouraged the writers to give her a more prominent role in the show.
Understandably, the audience was heartbroken when Lexie, along with Meredith, Derek Shepherd (Patrick Dempsey), Cristina Yang (Sandra Oh), Mark Sloan (Eric Dane), and Arizona Robbins (Jessica Capshaw) faced a terrible plane crash in season eight.
When Mark finally tracked down Lexie, she was trapped under airplane debris. He tried to help her out, but Lexie confirmed that she didn't have much time. The sentimental conversation between them in the last few minutes before her death aimed to provide some closure to fans, but they still felt that Grey's Anatomy didn't do full justice to Lexie's character.
5) Cristina Yang: season 10, episode 24

One of the best things about Grey's Anatomy is the dynamics between the main characters, especially the friendship between Meredith and Cristina. So, it was a big shock for fans when Sandra Oh's character decided to leave the hospital to pursue a top cardiothoracic job in Switzerland at the end of season 10.
Both Meredith and Cristina had seen each other through countless tough times, and therefore, the audience was left questioning how Meredith's life would change without Cristina's presence. As expected, the following seasons of Grey's Anatomy addressed the loneliness Meredith experienced after losing "her person".
Like Meredith, fans of Grey's Anatomy also moved on with time, but it cannot be denied that Cristina's exit left a big void that hasn't been filled to date.
6) Derek Shepherd: season 11, episode 21

A big part of Grey's Anatomy's narrative revolves around the relationship between Meredith and Derek. Over the seasons, their relationship went through many ups and downs, but fans were hopeful that the duo would make it work in the end. But everything comes to a screeching halt when Derek gets into a car accident.
This Grey's Anatomy episode kept viewers on the edge of their seats because they could see everything happening from Derek's point of view. The doctors attending to the emergency made several mistakes that Derek could identify but couldn't point out due to his injuries, which made it even more harrowing for the audience.
Eventually, Meredith makes the heartwrenching decision to take him off life support. Fans around the world mourned alongside Meredith as they said goodbye to one of their favorite characters on the show.
7) Alex Karev: season 16, episode 8

Like Cristina, Alex Karev's exit from Grey's Anatomy was not related to death. Justin Chambers' character stood out from the very beginning because he never minced his words. Despite his temper and dismissive behavior, fans were drawn to the complex character because it was obvious that there was much more underneath the surface.
Fans were upset because the episode of Alex's exit didn't even feature the actor on screen. It was revealed that Alex had reconnected with Izzie and discovered that she had used their embryos to have twins. He then decided to move to Kansas to be with them.
It's disappointing that the audience didn't get to say their proper goodbyes, but the fact that the story arc circled back to the beloved Alex and Izzie pairing did earn praise from long-term fans.
There is no doubt that Grey's Anatomy has been an emotional rollercoaster, and these shocking character exits heightened the tension and drama to keep viewers coming back for more.