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".

It was posted on Thursday on Twitter by the south Belfast politician.
A number of politicians from Northern Ireland tweeted pictures of their ballot papers.
However, Ms Hanna's photo showed her daughter holding a pencil with her hand, appearing to mark a ballot paper for the EU Referendum.
A spokesperson for the Electoral Office said: "We would strongly discourage anyone from taking photographs inside the polling station."
EU Referendum results
The spokesperson added that "the requirement for secrecy around the conduct of the ballot is set out in the Representation of the People Act (1983)".
The BBC contacted the SDLP press office to get a comment from Claire Hanna but is still awaiting a reply.
However, in a Facebook post, Ms Hanna said: "This is literally the stupidest article I have ever read on what is the absolute opposite of a slow news day."
Northern Ireland has voted to remain in the EU Referendum by a majority of 56% to 44%.
However, the UK, as a whole, has voted by a narrow margin to leave the EU.
Overall, 440,437 people in Northern Ireland voted to Remain in the EU and 349,442 to Leave. Out of 18 constituencies, 11 voted to stay in the European Union.
The turnout in Northern Ireland was 62.7% with 789,879 people voting in the referendum.
Get the results in full.

The emergency services were called to Boclair Academy in Bearsden on Friday morning after a "strange smell" was detected in the building.
East Dunbartonshire Council said all pupils were safe and had been taken to nearby Killermont Primary School.
Boclair Academy was later declared safe after a leak from emergency lighting was identified as the source.
After the evacuation, arrangements had been made for pupils to sit their National 5 Modern Studies exam at Bearsden Academy.
However, the council later said the exam would take place as originally planned at Boclair Academy.
The school is expected to open again as usual on Monday.
The US government says it has released six Guantanamo Bay detainees and sent them to Uruguay for resettlement.
[NEXT_CONCEPT]
The SDLP MLA Claire Hanna has tweeted a photo of her daughter appearing to mark her referendum ballot paper in a polling station booth.
[NEXT_CONCEPT]
Exams are set to go ahead as planned at a secondary school which was evacuated due to a chemical leak.