10 ‘Grey’s Anatomy’ characters whose deaths left fans devastated

In its 20-season-plus run, Grey’s Anatomy has become infamous for killing off prominent characters. The premiere of the latest instalment, season 22 (2025), saw the death of Dr Monica Beltran. Some other characters who were killed off on the show tragically include Dr George O’Malley, Dr Derek Shepherd and Denny Duquette.

Grey’s Anatomy is one of the longest-running dramas in US television history. The popular TV show, which first premiered in 2005, is now in its 22nd season. In the past 20 years, Grey’s Anatomy has garnered much love and admiration for its memorable characters, powerhouse performers (especially in the first few seasons), and, of course, some truly iconic songs. But above all, it’s perhaps best known for killing off some of its most beloved characters in truly shocking ways.

But first, brace yourselves for spoilers in case you haven’t watched the latest season, because the show has once again killed off a major character right at the beginning of the 22nd season. Yes, Dr Monica Beltran (played by Natalie Morales) was confirmed dead in the season 22 premiere, much to fans’ dismay, after she sustained severe injuries in the season 21 finale.

In fact, over the years, Grey’s Anatomy has gained a reputation for killing off major characters. Now, whether these deaths were simply for shock value to keep the ratings up, or whether they genuinely served to drive the plot forward — well, we’ll let you be the judge of that.

And while many characters have been killed off — such as Dr George O’Malley (played by T.R. Knight) and Derek Shepherd (played by Patrick Dempsey) — several main characters have also exited the show as the actors moved on to pursue other projects. For instance, Sandra Oh, who played Dr Cristina Yang, left after 10 seasons, and Katherine Heigl, who portrayed Dr Izzie Stevens, departed in season six. Ellen Pompeo, who plays the protagonist Dr Meredith Grey, is one of the few original cast members still remaining on the show.

So, let’s take a look at some of the most tragic and heartbreaking deaths of major characters in Grey’s Anatomy over the years.

Major characters from Grey’s Anatomy who still haunt us after their shocking deaths

1 /9

Dr George O’Malley

Played by: T.R. Knight

First appearance: Season 1, episode 1, “A Hard Day’s Night”

Last appearance: Season 17, episode 4, “You’ll Never Walk Alone”

Died in: Season 6, episode 1, “Good Mourning”

Cause of death: Hit by a bus

This is perhaps the most shocking death in Grey’s Anatomy that continues to haunt fans to this day. His death was totally unexpected, and to make matters worse, the season ended on a cliffhanger with people having to wait until the next one to find out if he had survived.

Spoiler: He didn’t.

After being hit by a bus, George is rushed to the ER, where his colleagues fail to recognise him due to his severely disfigured face. When they eventually realise his identity, it’s too late. George flatlines and is declared brain dead as a result of the serious injuries he sustained.

Image courtesy: IMDb

2 /9

Dr Derek Shepherd

Played by: Patrick Dempsey

First appearance: Season 1, episode 1, “A Hard Day’s Night”

Last appearance: Season 17, episode 13, “Good As Hell”

Died in: Season 11, episode 21, “How to Save a Life?”

Cause of death: Brain injury due to a car accident

Dr Derek Shepherd, nicknamed McDreamy, was another character whose death hit fans hard. His love story with Meredith is one for the ages, which makes his passing all the more tragic.

While driving to Washington, Derek is involved in an accident. However, it is not the accident itself that proves fatal. Derek sustained a brain injury in the crash, but his death could have been prevented if it had been diagnosed and treated in time. The hospital he is taken to fails to perform a timely CT scan, a delay that ultimately leads to his death.

His soulmate, Meredith, reels from his loss for many years, even confronting one of the doctors who failed to provide him with proper treatment and care. What makes his death even more heartbreaking is that the decision to take him off life support ultimately lies with Meredith.

3 /9

Denny Duquette

Played by: Jeffrey Dean Morgan

First appearance: Season 2, episode 13, “Begin The Begin”

Last appearance: Season 5, episode 23, “Here’s To Future Days”

Died in: Season 2, episode 27, “Losing My Religion”

Cause of death: Complications after a heart transplant

The death of any Jeffrey Dean Morgan character is difficult to process, but this one was particularly devastating due to the emotional love story between him and Dr Izzie. Denny needs a heart transplant, and Izzie, willing to do anything for the man she loves, makes a heartbreaking and ethically questionable decision: she deliberately allows his condition to worsen so he can move higher on the transplant list. In a desperate act, she even attempts to cut his LVAD wire, abandoning all medical ethics in the hope of saving him.

Eventually, Denny does receive a heart, and the couple is given a sliver of hope, until it’s cruelly snatched away when complications arise. Denny develops a blood clot and dies.

Image: courtesy IMDb/Grey’s Anatomy

4 /9

Dr Lexie Grey

Played by: Chyler Leigh

First appearance: Season 3, episode 24, “Testing 1-2-3″

Last appearance: Season 17, episode 10, “Breathe”

Died in: Season 8, episode 24, “Flight”

Cause of death: Plane crash

After her tumultuous relationship with her half-sister Meredith finally blossoms into a loving bond, Lexie is killed off.

She is on a plane with Meredith, Derek, Mark and others when it crashes. Crushed by parts of the wreckage, she dies at the scene. While the others are also gravely injured, they all survive, including Mark, who loves her. He stays with her as she takes her final breath.

Her death is all the more poignant due to her heartfelt monologue about her love for Mark just a few episodes before the crash.

5 /9

Dr Mark Sloan

Played by: Eric Dane

First appearance: Season 2, episode 18, “Yesterday”

Last appearance: Season 17, episode 10, “Breathe”

Died in: Season 9, episode 1, “Going, Going, Gone”

Cause of death: Injuries from a plane crash

Even though Mark appears to have survived the crash initially, he dies in the hospital after succumbing to his injuries. Perhaps he couldn’t live without Lexie, who died right in front of him.

Mark’s death hit Derek hard, as he was his best friend. In fact, Mark and Lexie’s deaths are even more tragic because their love story was left unfinished due to their untimely passing. Or perhaps they were soulmates, destined to die together. At the very least, that thought is a comforting one.

6 /9

Dr Monica Beltran

Played by: Natalie Morales

First appearance: Season 20, episode 3, “Walk on the Ocean”

Last appearance: Season 22, episode 1, “Only the Strong Survive”

Died in: Season 22, episode 1, “Only the Strong Survive”

Cause of death: Injuries from an explosion

The most recent shocking death on Grey’s Anatomy occurred in the season 22 premiere, where Monica was killed off. In the cliffhanger finale of season 21, which featured a gas explosion involving Monica and Link, viewers were left eager to learn the fate of these characters.

While Link survived, Grey’s Anatomy pulled a George O’Malley-style twist and killed off Monica in the first episode of the new season.

7 /9

Adele Webber

Played by: Loretta Devine

First appearance: Season 2, episode 2, “Enough Is Enough”

Last appearance: Season 9, episode 10, “Things We Said Today”

Died in: Season 9, episode 10, “Things We Said Today”

Cause of death: Heart attack

Grey’s Anatomy certainly knows how to give viewers false hope. Adele, the wife of Richard Webber, who was known to be suffering from Alzheimer’s disease, underwent surgery for a brain aneurysm. Although the operation was successful, she later died of a heart attack.

8 /9

Dr Reed Adamson and Dr Charles Percy

Played by: Nora Zehetner, Robert Baker

First appearance: Season 6, episode 5, “Invasion”

Last appearance: Season 6, episode 23, “Sanctuary”; Season 12, episode 11, “Unbreak My Heart”

Died in: Season 6, episode 23, “Sanctuary”; Season 6, episode 24, “Death and All His Friends”

Cause of death: Hospital shooting

Even though Reed and Charles were not regular characters in the series, their deaths were no less shocking or impactful. A shooter enters the hospital seeking revenge for his wife’s death, leaving everyone on edge. While specifically looking for Derek, he kills both Reed and Charles in this two-part series finale.

In fact, the season 6 finale is considered among the best of the entire show, thanks to the performances delivered by the cast.

Image: Courtesy IMDb/Grey’s Anatomy

9 /9

Henry Burton

Played by: Scott Foley

First appearance: Season 7, episode 10, “Adrift and at Peace”

Last appearance: Season 8, episode 10, “Suddenly”

Died in: Season 8, episode 10, “Suddenly”

Cause of death: Tumour

Another ethically questionable storyline in the show involves Henry Burton, a patient who needs a heart transplant but has no health insurance. This leads Dr Teddy Altman to marry him so that he can be covered under her health insurance.

In fictional books and television shows, insurance fraud is a popular trope where characters end up falling in love due to a marriage of convenience. The same happens with Henry and Teddy — they fall in love, which adds to the tragedy of Henry’s death following a failed surgery.

Note:

The information in this article is accurate as of the date of publication.

Frequently Asked Questions

How many major characters has ‘Grey’s Anatomy’ killed off so far?

As of 2025, ‘Grey’s Anatomy’ has killed off around a dozen major characters throughout its run, including Dr George O’Malley, Dr Derek Shepherd, Denny Duquette, Dr Lexie Grey and Dr Mark Sloan.

Who was the first major character to die in ‘Grey’s Anatomy’?

Denny Duquette was one of the first major characters to die in ‘Grey’s Anatomy’. He died in the season 2 finale.

Which ‘Grey’s Anatomy’ death shocked fans the most?

Dr George O’Malley’s death in ‘Grey’s Anatomy’ shocked fans the most as it was completely unexpected. The deaths of Dr Derek Shepherd, Dr Lexie Grey and Dr Mark Sloan were also devastating for fans.

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