The blind activist and his family boarded a flight to Newark, near New York, after being taken from a Beijing hospital to the capital's airport.
Mr Chen recently spent six days in the US embassy in Beijing after escaping house arrest in north-east China.
He has been offered a fellowship at New York university.
Chen Guangcheng, a self-taught lawyer who campaigned against forced abortions under China's one-child policy, was jailed for four years in 2006 for disrupting traffic and damaging property, and placed under house arrest after his release in 2010.
Earlier on Saturday, Mr Chen was picked up from the hospital where he was being treated for a foot injury and taken to Beijing airport, along with his wife and two children.
At the airport they were handed passports and allowed to leave. They boarded flight UA88 to Newark, New Jersey, which departed at 17:50 (09:50 GMT), more than two hours late.
"Thousands of thoughts are surging to my mind," Mr Chen told the Associated Press news agency from the terminal.
Referring to his supporters, he said: "I am requesting a leave of absence, and I hope that they will understand."
The state-run Xinhua news agency said Mr Chen had applied to study abroad "via normal channels in line with the law".
US state department spokeswoman Victoria Nuland said the administration was looking forward to welcoming 40-year-old dissident to the US, and expressed "appreciation for the manner in which we were able to resolve this matter".
Bob Fu, president of the US activist group China Aid and a key supporter of Mr Chen, told the BBC that the dissident was planning to stay in New York for two to three years.
"Of course he wants to spend some time to rest after seven years of brutal treatments at the hands of the Chinese local authorities," Mr Fu said.
'Reprisals'
With the activist on his way, both China and the US will want to put this extraordinary diplomatic dispute behind them, says the BBC's Martin Patience in Beijing.
Last month Mr Chen fled from house arrest in Shandong province.
According to media accounts, the blind activist climbed over the wall of the property with the help of his wife late at night.
When he landed on the other side he broke his foot. He is then said to have felt his way in the dark, stumbling and falling, to a nearby village when a friend took him into his home.
He was then driven hundreds of kilometres away to the American embassy. He took refuge there during a visit by US Secretary of State Hillary Clinton, who was in Beijing for high-level talks.
On 2 May, after six days at the embassy, he agreed to leave the compound, initially saying he wanted to stay in China.
He was taken to hospital for treatment. During his stay there he called the US Congress twice.
On 3 May he pleaded for help to leave China with his family, saying he feared for his safety, and on 16 May he called again, accusing Shandong authorities of harassing his family.
Mr Chen was offered a place to study law at New York University after Beijing said he would be allowed to apply to study abroad.
The US has said visas for Mr Chen and his family are ready.
However the activist has repeatedly warned that his friends and relatives could face reprisals once he has left.
Source: BBC News
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