Stanton, who will start for just the second time in his career, will fill in for Shaun Hill, who hurt a finger on his throwing hand against New England on Thursday.
Hill, who opened the season as the Lions' back-up, had replaced second-year starter Matthew Stafford who injured his shoulder in the season opener at Chicago.
"The guys around him are going to make plays. Other than a different number on the quarterback, there's not going to be any change there."
Zac Robinson will be Stanton's back-up after being claimed off waivers last month from Seattle.
Detroit (2-9) has lost four straight and is in last place in the NFC North.
(Reporting by Steve Ginsburg in Washington; Editing by Ed Osmond)