The actress will still narrate each episode, but will focus on her new Hulu project Orphan, inspired by the true story of Ukrainian-born Natalia Grace and her US adoptive parents who claimed that she was an adult “sociopath” pretending to be a child.
WATCH: Grey's Anatomy hits milestone 400 episodes
Ellen has long admitted that she had been trying to persuade show bosses to call it a day, and showrunner Shonda Rhimes previously shared that she does not see the show continuing without its lead actress.
The 52-year-old actress who has been playing Dr Meredith Grey on the show since it began in 2005, told Insider: "I’ve been trying to focus on convincing everybody that it should end. I feel like I'm the super naive one who keeps saying, 'But what's the story going to be, what story are we going to tell?'
"And everyone's like, 'Who cares, Ellen? It makes a gazillion dollars.'"
Ellen Pompeo has been playing Dr Meredith Grey on the show since 2005
It's unclear whether the show has a future past season 19 and if Ellen will return full time.
Original stars Ellen, Chandra Wilson and James Pickens Jr. continue to helm the show, and it remains ratings gold, named the fourth most-watched broadcast series across 2021-2022.
At the end of season 18, Grey Sloan Memorial Hospital was ordered to disband and rebuild the teaching program but also left the future of several fan favorites up in the air. Meredith, played by Ellen, chose to stay at Grey Sloan while others including Miranda Bailey, played by Chandra, chose to leave the hospital.