The Bolton Wanderers star, who suffered a cardiac arrest during an FA Cup tie in March, said he was devastated his footy career was over but had to put his health first.
The 24-year-old thanked the medical team who saved him and said he was grateful for all the support he has received.
Muamba said: “Since suffering my heart attack and being discharged from hospital, I have remained utterly positive in the belief I could one day resume my playing career and play for Bolton Wanderers once again.
“As part of my on-going recovery, last week I travelled to Belgium to seek further medical advice from a leading cardiologist.
“But the news I received was obviously not what I had hoped it would be and it means I am now announcing my retirement from professional football.
“Football has been my life since I was a teenage boy and it has given me so many opportunities.
"Above all else, I love the game and count myself very lucky to have been able to play at the highest level.
“While the news is devastating, I have much to be thankful for.
“I thank God that I am alive and I pay tribute once again to the members of the medical team who never gave up on me.
“I would also like to thank everyone who has supported me throughout my career, and the Bolton fans who have been incredible.
“I am blessed to have the support of my family and friends at this time.”
Muamba's heart stopped for 78 minutes after he collapsed on the pitch at White Hart Lane on March 17.
Millions on TV watched as medics from both teams and a heart specialist who rushed from the stands desperately battled to keep him alive.
Collapse ... Muamba suffered cardiac arrest on pitch
The midfielder even underwent a heart operation in Belgium last week as he set his sights on a comeback.
His fiancee Shauna tweeted a hopeful update to friends and family following the surgery.
She said: "Thank you guys for the support if it is Gods will @fmuamba will play again even better and stronger than before. Faith can move mountains."
But docs told him playing in the top flight could put too much strain on his heart and was not worth the risk.
A source said: “Fabrice is devastated as you can imagine.”
Miracle ... docs were amazed at Fab's recovery
“We are all hugely disappointed that Fabrice will be unable to return to his playing career but we have to be guided by the medical recommendations and the best interests of Fabrice.
“The most important thing is that Fabrice and his family have the rest of their lives ahead of them.”
Manager Owen Coyle said: “We have spoken with Fab and he knows we will always support him in whatever he wants to do and that we will always be here for him.
“He is obviously massively disappointed that he won’t be able to carry on his career, but everyone has seen what a fighter and strong person he is in mind and body.
“We know that he will go on to achieve great things and within all this disappointment, the most important thing is that he is here, alive, today.”
Star ... the midfielder was a key player for Bolton
Before the announcement, he cryptically tweeted: “KEEP SMILING PEOPLE.”
The star is now in line for a multi-million pound insurance payout.
Muamba's cardiac arrest was not the first time he has battled against the odds.
His family fled war in the Democratic Republic of Congo before seeking asylum in the UK.
Despite arriving in London aged 11 unable to speak English, he managed to get 10 GCSEs and three A-levels at school.
He then joined Arsenal FC’s youth academy in 2002 before moving to Birmingham and then Bolton in 2008.
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