The 24-year-old actor, who was recently Emmy nominated for his role in the BBC's adaptation of the Sally Rooney novel, will star alongside Oscar-winner Olivia Colman.
The film is based on the 2008 novel by Elena Ferrante, the beloved author of My Brilliant Friend - part of her best-selling Neapolitan novels.
According to The Hollywood Reporter, The Crown's Colman stars as an elegant college professor on a seaside summer vacation who becomes consumed by Nina and her young daughter as she watches them on the beach, only to be overwhelmed by fearful memories of early motherhood.
Forced to consider the unconventional choices she made as a young mother and the consequences they had for her family, she begins to unravel.
The impressive cast also includes Dakota Johnson, Chernobyl's Jessie Buckley, and Jackie's Peter Sarsgaard. Sarsgaard is married to Gyllenhaal, and the couple have two children together.
Gyllenhaal and Charlie Dorfman will produce with Talia Kleinhendler and Osnat Handelsman-Keren of Pie Films, which worked with Gyllenhaal on her compelling drama The Kindergarten Teacher.
"When I finished reading Elena Ferrante’s The Lost Daughter, I felt that something secret and true had been said out loud," Gyllenhaal has previously said.
"And I was both disturbed and comforted by that. I immediately thought how much more intense the experience would be in a movie theatre, with other people around. And I set to work on this adaptation.
"I find that the script has attracted other people interested in exploring these secret truths about motherhood, sexuality, femininity, desire. And I’m thrilled to continue my collaboration with such brave and exciting actors and filmmakers.”
Mescal had his breakout role as Connell in Sally Rooney's Normal People alongside Daisy Edgar-Jones. He most recently starred in Channel 5 thriller The Deceived.
Responding to the news, the star wrote on Twitter: "I'm a very excited boy!"
Filming has yet to begin.
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