Based on an award-winning play, first staged in 2012, it will be adapted by the play's own writer Samuel D. Hunter.
It's set in an apartment in rural Idaho, in which a man named Charlie, to be played by Fraser, is trying to eat himself to death.
Only visited by his friend and nurse Liz and Elder, a young mormon missionary, who hopes to save him spiritually, it's only when his estranged daughter Ellie returns that he sees hope of redemption.
Hunter told Deadline: “Adapting my play into a screenplay has been a real labor of love for me. This story is deeply personal and I'm very thankful it will have the chance to reach a wider audience.
“I've been a fan of Darren's ever since I saw Requiem for a Dream when I was a college freshman writing my first plays, and I'm so grateful that he's bringing his singular talent and vision to this film.”
It will be produced by indie studio A24.
The movie is the first from Aronofsky following 2017's controversial, critically polarising Mother!, starring Jennifer Lawrence and Javier Bardem.
Meanwhile, thanks in part to huge hits like the Mummy movies in the late 90s, these days Fraser more often appears in 'where are they now?' features than on screen.
However, a career resurgence appears to be on the cards. He’s currently starring in DC Comics series Doom Patrol, and will appear in No Sudden Move the star-studded new movie from Steven Soderbergh later this year alongside Don Cheadle, Benicio del Toro, David Harbour, Jon Hamm, Ray Liotta, Kieran Culkin, Noah Jupe, and Amy Seimetz.
Watch: How Brendan Fraser nearly became Superman