Fawzi al-Odah, 37, was released after a US review panel concluded he was not a "continuing significant threat".
He had been at the US facility in Cuba since 2002 after his arrest in Pakistan on suspicion of links to al-Qaeda and the Taliban - a charge he denies.
He had challenged America's right to detain him in the US Supreme Court.
Mr Odah boarded a Kuwaiti government plane on Wednesday morning US time.
"There's no bitterness, there's no anger," his lawyer Eric Lewis was quoted as saying by the Associated Press news agency.
"There's just excitement and joy that he will be going home."
The release came after Guantanamo's Periodic Review Board in July determined "that continued law of war detention of (Mr Odah) does not remain necessary to protect against a continuing significant threat to the security of the United States".
But he now faces at least a year at a militant rehabilitation centre in Kuwait, according to the terms of the release.
The Kuwaiti government had pushed hard for the release of all Kuwaiti detainees at Guantanamo.
Mr Odah had argued that he travelled to Afghanistan and Pakistan to teach the Koran and provide humanitarian aid.
He is the first inmate to be freed since May, when five Taliban detainees were exchanged for US Sgt Bowe Bergdahl, who had been kept by the insurgents in Afghanistan.
Mr Odah's release brings down the total number of inmates at the US naval base to 148.
The US opened the facility in January 2002, following the 11 September 2001 attacks in America.
President Barack Obama has repeatedly promised to shut it down.
One of the longest-held detainees at the US facility at Guantanamo Bay, a Kuwaiti man, has been sent home, officials say.