The English-born running back was due to return to the UK later this month with the Eagles facing Jacksonville Jaguars at Wembley on October 28.
However he was reportedly injured as the Super Bowl champions were beaten 23-21 by Minnesota Vikings yesterday.
The 25-year-old Ajayi had accumulated 29 yards on eight carries during that defeat though he missed a handful of snaps due to discomfort.
And NFL insider Ian Rapoport has now reported that the RB will miss the remainder of the 2018 NFL season.
Rapoport’s tweet read: “Why is #Eagles RB Jay Ajayi on Injured Reserve? He tore his ACL, source said. He’s out for the season and for someone who already had major knee issues, this is another one.”
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Ajayi shone for the Eagles last season after joining from Miami Dolphins.
He helped Philadelphia to their first Super Bowl title when they beat the New England Patriots 41-33.
Quarterback Nick Foles starred as MVP though Ajayi had rushed for 57 yards during the clash.
And Ajayi recently revealed what he got away with after bringing the Vince Lombardi Trophy to Pennsylvania.
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When asked the biggest perk of winning the Super Bowl, Ajayi said: “I’d probably say getting out of a ticket, a traffic ticket period.
“It was in Philadelphia. They gave me a warning instead of giving me a citiation.
“That kind of perk comes with bringing the Super Bowl to Philly so that was cool.
“They’ve shown us appreciation. We have the best fans in the world so it’s awesome to enjoy that environment.
“It makes it tough because they care so much so we have to make sure we are doing the right thing to succeed on the field.”