The "Snatched" star, who is heavily pregnant with husband Chris Fischer's baby, will join former "The Walking Dead" actor Steven Yeun, Richard Jenkins, Beanie Feldstein, and Jayne Houdyshell in the project.
"The Humans" playwright Stephen Karam will pen the film's script and also serve as director, reports Deadline.
The one-act play, which debuted on Broadway in 2016, focused on the Blake family's Thanksgiving holiday gathering, held at a run-down New York City apartment. The celebrations quickly ended as the relatives bickered about religion, illnesses, and economy worries.
It won four Tony Awards in 2016, including Best Play and Best Featured Actress in a Play for Houdyshell. She will reprise her role as family matriarch Deirdre for the big screen adaptation.
Top producer Scott Rudin will help to develop the film version. A projected release date has yet to be set.
"The Humans" will mark Schumer's first movie gig as a mother, and her first following romantic comedy "I Feel Pretty" last year (2018).
The news of her casting emerges shortly after the release of a new profile piece in The New York Times, in which Amy admitted she was eager to get back to work following her maternity leave as she wanted to take "control" of her projects once again.
"I like all the things I've done, but my favourite is when I'm in control. The last two movies I didn't write," the 37-year-old star shared, referring to "I Feel Pretty" and "Snatched". "I didn't really have anything to say. I now do."
She had tried to work through her pregnancy pains despite suffering from severe morning sickness condition hyperemesis gravidarum, but last month, she was forced to cancel the last few dates of her comedy stand-up shows on doctors' orders as she was no longer cleared to fly.