The actress, who has played Emily/Ofglen on all four seasons of the Hulu drama, announced she is exiting the show in a statement to E! News.
"After much thought, I felt I had to step away from "The Handmaid's Tale" at this time," Alexis said. "I am forever grateful to [creator] Bruce Miller for writing such truthful and resonant scenes for Emily, and to Hulu, MGM, the cast and crew for their support."
Alexis was nominated for an Emmy for each season of the series, winning the Guest Actress in a Drama Series trophy in 2017.
When viewers last saw Emily on the series, an adaptation of the classic Margaret Atwood novel, she and a group of escaped Handmaids murdered Commander Fred Waterford (Joseph Fiennes), who had orchestrated a plea deal that would let him walk in exchange for his becoming a spy in Gilead.
Season five of "The Handmaid's Tale" is expected to premiere on Hulu later this year.