The uncapped Williams, 24, was being touted for a possible openside role by England head coach Eddie Jones, but will now be out for up to three months.
James Haskell, Jack Clifford and Sam Jones were already on the injured list.
"It's bitterly disappointing with England on the horizon," said Leicester director of rugby Richard Cockerill.
England start their autumn campaign against South Africa at Twickenham on 12 November.
Williams was injured during the warm-up before last Saturday's game against Worcester Warriors.
It was initially hoped he had suffered nerve damage and would be fit for the European Champions Cup game with Glasgow Warriors on Friday.
The Zimbabwe-born, England-qualified forward broke a bone in his forearm last December and then broke it again in January, meaning his season ended five months early.
"Unfortunately he's re-fractured his arm that he broke last year. It will heal in 8-12 weeks," Cockerill told BBC Radio Leicester.
"It's the same arm and fracture site. Historically, these things are notoriously difficult to clear up. They have a history of coming back. They are very difficult injuries to shake off.
"We have done all the right things and he has done everything he can do but it is purely bad luck."
England have lost another flanker for the autumn series after it was confirmed Mike Williams has broken his arm for the third time in 12 months.