A Pentagon statement on Sunday identified the men as four Syrians, a Tunisian and a Palestinian.
All six had been detained as suspected militants with ties to al-Qaeda but were never charged.
Uruguayan President Jose Mujica decided to take the detainees on humanitarian grounds in March but the move was put off until after elections last month.
"The United States is grateful to the Government of Uruguay for its willingness to support ongoing US efforts to close the Guantanamo Bay detention facility," the Pentagon said in a statement.
President Barack Obama has pledged to close the camp in Cuba, which was opened in 2002 as a place to detain enemy combatants in America's war on terror.
Around half of the 136 men still in Guantanamo have been cleared for transfer but have nowhere to go because their countries are unstable or unsafe.
More than 50 countries have accepted former Guantanamo detainees.
The US named the prisoners released to Uruguay as Ahmed Adnan Ahjam, Ali Hussain Shaabaan, Omar Mahmoud Faraj, Abdul Bin Mohammed Abis Ourgy, Mohammed Tahanmatan, and Jihad Diyab.
They have been cleared for release since at least 2010 but they could not be sent home, according to the Associated Press.
In Latin America, El Salvador is the only other country to have given Guantanamo prisoners sanctuary, taking two in 2012.
An October opinion poll showed 58% of Uruguayans were opposed to bringing in the prisoners.
President Mujica was himself held for over a decade in harsh prison conditions during Uruguay's period of military rule in the 1970s and 80s.
Reiterating his commitment to take the six prisoners on Friday, he said Uruguay was offering its hospitality to "human beings who have suffered a terrible kidnapping in Guantanamo Bay".
The US government says it has released six Guantanamo Bay detainees and sent them to Uruguay for resettlement.