Recovered patient Dr Kent Brantly thanked supporters for their prayers at a news conference. Nancy Writebol was discharged on Tuesday.
The two were brought to the US for treatment two 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.
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 he was working for 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.