Hartley is definitely out of England's opening Test against Fiji on November 10, as is Courtney Lawes, and he is expected to be sidelined for up to four weeks.
England coach Stuart Lancaster would not officially rule Hartley out of the Tests against Australia, South Africa and New Zealand but his involvement seems unlikely.
Hartley captained England to a 14-14 draw against South Africa in June, when Chris Robshaw was out with a broken hand, and his presence will be sorely missed.
"Dylan was one of our key players in the Six Nations and in South Africa, there is no doubt about it," Lancaster said.
"He was desperate to part of a massive autumn series and to have it snatched away so close to being here is cruel for him.
"It is not unrealistic for him to get back in the mix, but it is going to take some work. A lot of things have to happen before then.
"We have got to get him some game-time for Northampton before we can pitch him into international rugby, particularly if you look at our last two games against South Africa and New Zealand."
England will be choosing between the uncapped Tom Youngs and David Paice, who won two caps off the bench in New Zealand four years ago, for the hooker's jersey this autumn.
Lancaster has no qualms about pitching either into the Test environment.
"We have had other players who have been in that situation. Tom Croft was one of our key players in the Six Nations and he wasn't available for (the tour of) South Africa but Tom Johnson took his opportunity," Lancaster said.
"Hopefully that can happen again. One thing I would say about trusting players who haven't got that much experience is that we have always gone with our gut instinct and to date they haven't let us down.
"Youngs has been playing well. He has been given big responsibility by Leicester in the Premiership and in Europe.
"David has matured as a player. He has had his ups and downs but I spoke to him today and he is excited. He said he is ready to stake his claim."
Lawes is also out with a knee injury, although he is anticipated to be out for up to a fortnight.
London Irish centre Jonathan Joseph is doubtful for the Fiji game with an ankle problem, but England expect Joe Marler to have recovered from a hamstring injury in time.
Lancaster described Chris Robshaw's appointment as a "no-brainer", although it was only made official once the squad arrived in camp at St George's Park.
Robshaw did briefly fear for his participation this autumn after being accidentally kicked in the face by Joseph in Harlequins' Aviva Premiership win against London Irish.
"I was slightly worried," Robshaw admitted.