The Vikings announced Saturday that Peterson had been downgraded on the injury report from doubtful to out and would not travel with the team to Atlanta to play the Falcons. This will be only the fourth game in Peterson's five-year NFL career that he will miss.
Toby Gerhart will be the featured runner in Peterson's place.
Peterson has not practiced since hurting his left ankle Sunday against Oakland. He was carted off, and X-rays were negative.
An MRI on Monday showed a Grade-1 high-ankle sprain, the least severe of the three categories, and he had been in a walking boot for three days this week.
Peterson is sixth in the NFL in rushing with 872 yards. He's tied with Philadelphia's LeSean McCoy with a league-leading 12 touchdowns.
Peterson was out of his walking boot Thursday and did some pool work. He tested the ankle again Friday but couldn't practice. He walked out to watch individual group drills at the Vikings' facilities before walking off the field with head trainer Eric Sugarman.
At 2-8, Minnesota has little incentive to rush its franchise back to return. Peterson signed a seven-year, $100 million contract extension during the preseason.
The Vikings also waived wide receiver Stephen Burton Saturday and signed tight end Allen Reisner from the practice squad with their top two tight ends hurting. Kyle Rudolph is doubtful because of a bruised quadriceps, and Visanthe Shiancoe is questionable due to a strained hamstring.
Information from The Associated Press was used in this report.