The 24-year-old, signed from Manchester United on deadline day in September 2014, last played for the Gunners in April, missing both the FA Cup final and end-of-season internationals.
Despite hopes Welbeck would be able to recover from bone bruising around the knee, Arsenal announced in a statement on Thursday the player had needed an operation and was now set for an extended spell of rehabilitation.
Arsenal manager Arsene Wenger had hoped the forward would be available soon after the international break
However, following an increased training schedule, it was decided surgery would be needed.
A statement from Arsenal read: "Danny Welbeck has undergone surgery on his left knee after being unable to sufficiently step up his rehabilitation work.
"The striker has been working throughout the summer to recover from the injury sustained at the end of April.
"It had been hoped he would avoid surgery, but after increasing his training workload, the injury to his cartilage did not respond as well as hoped and the decision was taken last week for him to undergo surgery by a leading specialist in the field.
"Danny is now expected to be out for a period of months and everyone at Arsenal wishes him well."
With the decision to operate having come last week, there would have still been time for Arsenal to move in the transfer window to bolster the attacking options.
Arsenal had long been linked with a move for first Karim Benzema at Real Madrid and then Uruguayan forward Edinson Cavani from Paris St Germain.
However, the deadline passed with no further additions to Wenger's squad apart from veteran goalkeeper Petr Cech, who arrived earlier in the summer from Chelsea.
The Gunners recovered from losing their opening Barclays Premier League match at home to West Ham, winning two of the three games since.
Midfielder Jack Wilshere continues his recovery from a hairline fracture in the left fibula and could be back in contention when domestic action resumes at home to Stoke on September 12.
With Welbeck now sidelined for an extended spell, more opportunities could be forthcoming for Theo Walcott to operate in his preferred central role.
The England forward started ahead of Olivier Giroud at Newcastle, but failed to find the target with the chances created for him.
Walcott, 26, has confidence he can perform wherever selected across the Arsenal frontline.
"I think you'll see a mixture of me playing in those three positions, on the left, right and centre, depending on how the game is and who the opposition is
That's why the manager is the best man to pick his team
I've shown the manager what I can do on the left, right and centre," Walcott said in an interview on the Arsenal Weekly podcast
"It's obviously well documented that I want to play up front but there's a lot of competition for places here
I will do my best in any position when I am given the opportunity to play for this club
I will always be judged on goals and assists but I feel like I would score a lot of goals up front."
The news of Welbeck's extended absence after Arsenal had failed to bring in another striker during the transfer window generated much debate among Gunners fans on social media
Former Arsenal midfielder Paul Merson believes supporters are right to raise questions
Speaking to Sky Sports, the one-time England international said: "It cheats the fans
The fans think 'what are we coming for? We turn up every week, we pay the highest prices and what for? Top four? We might get a day out at Wembley again in the FA Cup.' Wow-wee
"If you're an Arsenal season ticket holder, you're paying top dollar
It's their money
It's the fans' money
It's not Arsene Wenger's money
It's not the club's money
It's the fans' money that they've paid to buy players.
"The whole idea of going to this big stadium that holds 60,000 people was to bring in top quality players
I don't know [why Arsenal aren't spending the money].
"Just put in a bid for Benzema
£75m
If Real Madrid turn around and say 'we're not selling him', you can't argue with that
You've put in a bid and if they turn it down or the lad doesn't want to come, that's the way it goes
But show something."
Source : PA
Source: PA