The number eight tore cartilage in his right knee during Saturday's 27-14 win over Argentina and after having an operation to cure the problem, has now been ruled out for at least three months.
It means he will now definitely miss the final Autumn International against Australia and is a major doubt for the Red Rose's opening Six Nations clash with France on February 4.
Vunipola has been a key member of the England side in recent months, establishing himself at the back of the scrum and playing a leading role in the Grand Slam victory and the summer whitewash of the Wallabies.
He has also enjoyed both domestic and European success with Saracens and Jones admits losing the powerful back-rower is a huge blow, although he has backed the rest of his squad to adapt.
"Billy's been absolutely fantastic for England over the last 11 months and we wish him a quick recovery," he said. "He's a very influential player in the set-up and there's no doubt he'll be missed for the game against Australia.
"We've had five or six frontline players missing throughout the series, so I've no doubt we'll adapt and work that little bit harder this week. I'm sure the players will respond to this by going up a level and peak for this game."