Team England announced the 31-year-old double Olympic and world champion, who was due to go for gold over 5,000 and 10,000 metres in Glasgow, had made good progress on his recovery from a recent illness, but had withdrawn to focus on getting back to full fitness in time for next month's European Championships in Zurich.
The news is a major blow to the Games, coming the morning after they launched with a spectacular opening ceremony at Celtic Park.
Farah said: "I have taken the tough decision to withdraw from the Commonwealth Games. The sickness I had two weeks ago was a big setback for me."
The Londoner, who was set to be one of the biggest stars in Glasgow, pulled out of his last two races - the Sainsbury's Glasgow Grand Prix at Hampden Park and last Sunday's Anniversary Games - after being admitted to hospital in the United States with abdominal pains.
He has been training hard at his altitude base in Font Romeu in a bid to be fit for the Games, but they have come too soon. The 5,000m final takes place on the first evening of the athletics programme on Sunday.
Farah added: "Training is getting better here in Font Romeu but I need another few weeks to get back to the level I was at in 2012 & 2013.
"I really wanted to add the Commonwealth titles to my Olympic and World Championships but the event is coming a few weeks too soon for me as my body is telling me it's not ready to race yet. Best wishes to my fellow athletes in Glasgow."
Team England chef de mission Jan Paterson said: "It is a real blow for any athlete to miss out on a major championships through injury, but to have fought so hard to regain full fitness and to have to take such a difficult decision at this stage is particularly hard. We wish Mo all the very best and hope to see him back to his peak very soon."
Farah's withdrawal comes three days after Katarina Johnson-Thompson, new mother Jessica Ennis-Hill's heir apparent, was forced out by a foot injury.
It means long jumper Greg Rutherford, who has himself withdrawn from his last two competitions for fitness reasons after struggling with a knee problem, is the only member of the golden trio from Super Saturday at London 2012 left in the England team.
Farah, who is in the Great Britain team for the 5,000m and 10,000m for the Europeans, which get under way on August 12, has raced only once on the track this year - over 5,000m at the Portland Track Festival in June.
His previous race had been a chastening marathon debut on the streets of London when he came home in eighth place.
Games boss David Grevemberg has spoken of his disappointment after Mo Farah pulls out of the Games. The star runner revealed this morning that he would no longer be competing during the Commonwealth Games due to illness.
Speaking this morning, Mr Grevemberg said: "There's no question that we are disappointed that Mo Farah announced this morning that he would not be competing in the Commonwealth Games.
"We're very disappointed for Mo, we knew how much he wanted to be here and we wanted to provide him with a fantastic welcome.
"I know he is disappointed that he won't be here.
"He has expressed that he wishes he would be able to come.
"We wish Mo a speedy recovery and hope he is in fighting form soon.
"I'm sure there will be some disappointed people but there are plenty of great athletes coming and training here."
Steve Cram, a three-time Commonwealth champion, told BBC Sport: "It's hugely disappointing for Mo and the event. We knew he had been struggling. He's just run out of time to be in shape and I was really hoping he would have run the 10,000m at least.
"Running the marathon earlier in the year has upset his normal pattern and had an impact on his summer.
"He knows how hard the 5,000m and 10,000m are going to be here, so he didn't want to put himself at the risk of not winning.
"It's not like the Europeans, where the competition is not particularly strong. He would not have wanted to come here and not be at his best, but he'll be a big miss."