"After six years in this role, Mr Clooney feels it is time to retire his official role as messenger of peace," UN spokesperson Stephane Dujarric confirmed on Monday.
"The competing demands on their time from their professional and advocacy lives sometimes make it difficult for high-profile individuals to carry out a formal United Nations role."
He then congratulated George on his engagement to human rights lawyer Amal Alamuddin, which has been confirmed by the actor's mother and father as well as Amal's employer, London's Doughty Street Chambers.
George, 52, was made a messenger of peace in 2008 after his work to raise awareness about the violence in the Darfur conflict, and his advocacy for aid for the millions of people displaced by the fighting there.
In the role, he travelled to the Democratic Republic of Congo, as well as South Sudan. And Mr Dujarric said that UN Secretary-General Ban Ki-moon hoped the actor would be involved with the organisation again at some point in the future.
The news comes as George's parents spoke of their joy at the surprising news that their son was going to tie the knot after a whirlwind romance.
"We are thrilled for them," Nick Clooney told RadarOnline. "We love Amal. We think they’re a wonderful match and wish them well.
His feelings were echoed by George's mum Nina, who confirmed the couple's engagement on Monday.
"I like her very much," the 74-year-old said, adding: ""You can say I'm extremely happy, Amal's a lovely girl.
"We weren't at all surprised when they told us they were engaged, and we couldn't be happier for them. On an intellectual level, they are equals. That is very important to him. Amal's world couldn't be more different from the Hollywood lifestyle."
Asked by MailOnline if Amal was very similar to the other girls George has dated, she replied resoundingly with: "Heavens, no! She's a lawyer, she is brilliant, she is a very bright woman and at the very top of her career. They also share a sense of fun, a sense of humour and they are both very caring people."