"Sadly, I'm no longer able to commit to Barbie due to scheduling conflicts," the actress said in a statement.
"The film has so much promise, and Sony and Mattel have been great partners. I'm bummed, but look forward to seeing Barbie on the big screen," she continued.
"We respect and support Amy's decision," a spokesperson for Sony added. "We look forward to bringing Barbie to the world and sharing updates on casting and filmmakers soon."
The live-action adaptation of Barbie was expected to start production this summer, Variety reported.
Previously, Schumer had fought back against critics of her casting in the Barbie film as detractors claimed that the comedian did not fit the iconic doll's slim appearance and signature look.
"They can scream as loud as they want. We can't hear them because we are getting [expletive] done. I am proud to lead by example. "I say if I'm beautiful, I say if I'm strong. You will not determine my story. I will," she wrote on social media in response.