The Beverly Hills 90210 and Riverdale star never recovered after being rushed to hospital on Wednesday.
He passed away this morning at St. Joseph's Hospital in Burbank surrounded by his family – including Jack and Sophie and fiance Wendy Madison Bauer.
His rep said: "Actor Luke Perry, 52, passed away today after suffering a massive stroke.
"The family appreciates the outpouring of support and prayers that have been extended to Luke from around the world, and respectfully request privacy in this time of great mourning.
"No further details will be released at this time."
Luke had been sedated to allow his brain to recover but the damage was too extensive, TMZ reports.
The US actor first shot to fame in the '90s, playing Dylan McKay in popular TV series Beverly Hills, 90210.
However, most recently Luke has found prominence playing Archie's dad Fred Andrews in hit show Riverdale, and the star was only recently spotted filming scenes on the Warner Brothers Hollywood lot.
He had also shot a role in Quentin Tarantino's upcoming Charles Manson film Once Upon a Time in Hollywood.
On the same day that Luke suffered his stroke, Fox announced that they are rebooting Beverly Hills, 90210.
The star was yet to sign on to the project, despite his former costars – including Tori Spelling, Jennie Garth, and Brian Austin Green – already being confirmed.
Luke is father to two children, 22-year-old Jack, and 18-year-old Sophie, who he shares with his ex-wife Rachel Sharp.
RISE TO FAME
He was born in Ohio in 1966 but moved to LA shortly after finishing high school to pursue a career in acting.
Luke auditioned for 215 acting jobs in New York before landing a role in an advert and later appearing in in the music video "Be Chrool to Your Scuel" for the band Twisted Sister alongside Alice Cooper.
He appeared in daytime soaps Loving and Another World but in 1990, he successfully auditioned for brooding millionaire's son Dylan McKay in 90210.
While starring on the teen drama, he won a supporting role in the original film version of Buffy the Vampire Slayer and cemented himself as a 90s heartthrob.
But in 1995, he decided to leave 90210 to focus on more adult roles and appeared in films Invasion, Riot and The Fifth Element.
Three years later, he returned to 90210 because of financial reasons.
He later said of the role: "I'm going to be linked with him until I die, but that's actually just fine. I created Dylan McKay. He's mine."
OTHER ACTING ROLES
As well as his acting, Luke was also known for his voiceover work and played himself – and Krusty the Clown's half-brother – in The Simpsons in 1993.
He voiced himself in an episode of Johnny Bravo and parodied himself again in Family Guy where he was branded gay by Peter and sued the family.
But in 2017 after dwindling appearances on broadway, he landed the role on Fred Andrews on CW series Riverdale.
The actor played main character Archie's dad on the Netflix show.
In 2015, the star spoke out to urge his fans to test for colon cancer after a colonoscopy revealed that he had precancerous growths.
The growths were removed and Luke became an advocate for getting tested, with the actor previously telling Fox News: "Right now, there are 23 million Americans who haven’t been screened who need to be screened.
"If I had waited, it could have been a whole different scenario.
"When I heard that this was the most detectable cancer that we know of yet it’s the second most lethal, I just couldn’t figure out why that was and I wanted to get out there and tell people about it."
'MY HEART IS BROKEN'
Tributes from devastated celebs have begun flooding in for the star after his tragic death today.
Molly Ringwald, who played his wife on Riverdale, said: "My heart is broken. I will miss you so much Luke Perry. Sending all my love to your family. #LukePerry."
Frozen actor Josh Gad said: "Heartbreaking. Absolutely heartbreaking. RIP #LukePerry."
Nancy Sinatra tweeted: "Oh, dear, I'm so sorry. Gone way too soon. Godspeed Luke Perry."
Luke's death comes after Prodigy singer Keith Flint was found dead in a suspected suicide at his home aged 49.
The iconic singer, from Essex, was discovered at around 8am this morning after police and paramedics were called to the property.
And in another tragic death, it was announced Australian Idol star Kate Cook had passed away aged 36.
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