Dr Kent Brantly, 33, thanked supporters for their prayers at a news conference in Atlanta. Nancy Writebol, 59, was discharged on Tuesday.
The two were brought to the US for treatment three weeks ago.
The outbreak has killed more than 1,300 people in West Africa, with many of the deaths occurring in Liberia.
“Today is a miraculous day,” said Dr Brantly, who appeared healthy if pallid as he addressed reporters on Thursday at Emory University hospital.
“I am thrilled to be alive, to be well, and to be reunited with my family. As a medical missionary, I never imagined myself in this position.”
He said Ebola “was not on the radar” when he and his family moved to Liberia in October.
After his family returned to the US as the Ebola outbreak tore through West Africa, he continued to treat Ebola patients and woke up on 23 July feeling “under the weather”.
Dr Brantly said he lay in bed for nine days, getting progressively sicker and weaker. On 1 August, he was flown to Atlanta for treatment at Emory.
Emory infectious disease specialist Dr Bruce Ribner said after rigorous treatment and testing officials were confident Dr Brantly had recovered “and he can return to his family, his community and his life without public health concerns”.
The group for which he was working in Liberia, Samaritan’s Purse, said they were celebrating his recovery.
“Today I join all of our Samaritan’s Purse team around the world in giving thanks to God as we celebrate Dr Kent Brantly’s recovery from Ebola and release from the hospital,” Franklin Graham said in a statement.
Nancy Writebol’s husband David said in a statement that she was free of the virus but was significantly weakened.
The family decided to leave the hospital privately in order to allow her to rest and recuperate.
Meanwhile, South Africa on Thursday said non-citizens arriving from Ebola-affected areas of West Africa – the countries of Guinea, Liberia and Sierra Leone – would not be allowed into the country.
And police in Liberia’s capital, Monrovia, fired live rounds and tear gas during protests after a quarantine was imposed to contain the spread of the deadly virus.
Residents of the capital’s West Point slum area said the barbed wire blockade stops them buying food and working.
There is no cure for Ebola, one of the deadliest diseases known to humans, with a fatality rate in this outbreak of 50-60%.
But both Dr Brantly and Mrs Writebol received an experimental treatment known as ZMapp.
The drug, which has only been made in extremely limited quantities, had never been tested on humans and it remains unclear if it is responsible for their recovery.
ZMapp was also given to a Spanish priest, who died, and three Liberian health workers, who are showing signs of improvement.