The 23-year-old was attempting to bring the ball down between two Revolution players in the middle of the pitch when he went to ground clutching his ankle.
Goal understands that he has suffered a suspected Achilles injury, which puts his participation in the Europa League decider in severe doubt.
He had only been introduced as a substitute at half-time as Maurizio Sarri made a host of changes at the interval at the Gillette Stadium in Foxborough, but the England international lasted just 22 minutes before going down with the injury.
The midfielder had to leave the stadium on crutches, fuelling suggestions that he will not be ready to race Arsenal in Baku on May 29.
Loftus-Cheek has had a breakout season for the Blues and scored for the club in the second leg of their Europa League semi-final tie against Eintracht Frankfurt - a game they would dramatically win on penalties.
Following that match, in which the midfielder was substituted to a chorus of boos from the Premier League club's supporters, he backed his manager's decision, telling reporters: "I've played a lot in these last few weeks, more than I've done in my career.
"So I think I have to pay attention to my body and take care of myself because I don't want another injury."
Chelsea picked a strong line-up for the post-season charity match against New England, with the 'Final Whistle on Hate' game expected to raise over $4 million to benefit organizations geared toward fighting racism in sports.
Eden Hazard, Pedro, David Luiz, Ross Barkley, Jorginho and Olivier Giroud were among the starters, with Gonzalo Higuaín, Loftus-Cheek, Willian and Cesar Azpilicueta all coming on at the break.
The Blues would go on to claim a comfortable 3-0 win, with England midfielder Barkley opening the scoring just three minutes in.
A diving header from Giroud made it 2-0 before the break before Barkley rounded off the scoring just after the hour mark.
But, with the match meaning little to either side in competitive terms, both clubs would have hoped to have avoided any injury issues.
Blues fans will now be desperately hoping that the injury sustained by Loftus-Cheek is not as serious as it seems, with just under two weeks to go until the showpiece meeting with the Gunners in Azerbaijan.