Dr. Martin Salia, a native of Sierra Leone and a permanent U.S. resident, was suffering from advanced symptoms, including kidney and respiratory failure, when he arrived at the Nebraska Medical Center on Saturday, the hospital said in a statement.
Hospital officials had said he was seriously ill when he was airlifted to the United States from West Africa.
"Dr. Salia was extremely critical when he arrived here, and unfortunately, despite our best efforts, we weren't able to save him," Dr. Phil Smith, medical director of the Biocontainment Unit at Nebraska Medical Center, said in a statement on Monday.
Salia, 44, was chief medical officer at United Methodist Kissy Hospital in Freetown, Sierra Leone, when he tested positive last week for Ebola, according to the United Methodist Church's news service.
The news service said it was unclear how or where Salia contracted the virus. He worked at several other medical facilities in addition to Kissy Hospital.
The church's news service said Salia has never practiced medicine in the United States. He trained as a doctor in Sierra Leone's College of Medicine and Allied Sciences, his wife said.
His evacuation was at the request of his wife, an American who lives in Maryland and who has agreed to reimburse the U.S. government for any expense, the State Department said.
Salia was the third Ebola patient treated at the Nebraska Medical Center. His treatment included a dose of convalescent plasma and ZMapp therapy, as well as being placed on dialysis, a ventilator and multiple medications to support his organs, the hospital said.
The two other Ebola patients treated by the hospital were infected in Liberia and recovered from the disease.
The current outbreak of Ebola is the worst on record. It has killed at least 5,177 people, mostly in Sierra Leone, Liberia and Guinea, according to the latest figures from the World Health Organization.