Doctors declared her brain dead at 1:25 p.m., said Duke University Medical Center spokesman Richard Puff.
She was kept on life support through the afternoon so family and friends could say goodbye, the hospital said in a statement. Medication to keep her heart going was discontinued at 5 p.m.; her heart stopped seven minutes later and a ventilator was then turned off.
Renee McCormick, a spokeswoman for a charity created to pay Jesica's medical bills, said the Santillan family didn't know until then that doctors were taking her off life support.
"They were hysterical," McCormick said. "The family's been treated so poorly. They're very hurt. These are human beings."
A family lawyer said earlier they didn't want to remove Jesica from life support until an outside doctor verified she was brain dead. He could not be reached later Saturday.
Jesica, 17, whose own heart had a deformity that kept her lungs from getting oxygen into her blood, received a heart-lung transplant Feb. 7. But because of human error, the organs were of a different blood type, and her body rejected them.
She was near death by the time the second set was placed in her body early Thursday. By early Friday, the newest organs were performing well but Jesica's brain was swelled and bleeding.
In the first operation, Dr. James Jaggers implanted organs from a donor with type A blood, rather than Jesica's O-positive. In a letter to the United Network for Organ Sharing, which matches patients with donated organs, Duke officials said Jaggers and Carolina Donor Services, a procurement agency, failed to share information about her blood type.
Jaggers, in his first public remarks, said Saturday he had hoped Jesica would be "one of those lucky few" awaiting heart-lung transplants who actually receive the surgery and do well.
"Unfortunately, in this case, human errors were made during the process" to match the organs with the patient, he said in a taped statement released by Duke.
"I hope that we, and others, can learn from this tragic mistake and move forward to make the process safer and available to more of those in need. To do otherwise would fail to properly honor Jesica and her memory."
Family lawyer Kurt Dixon said Jesica's parents and supporters, who had remained with her through her hospitalization, would not be available for comment.
"All of us at Duke University Hospital are deeply saddened by this," Dr. William Fulkerson, the hospital's chief executive officer, said Saturday. "We want Jesica's family and supporters to know that we share their loss and their grief. We very much regret these tragic circumstances."
Relatives have said her family paid a smuggler to bring them from their small town near Guadalajara, Mexico, to the United States so she could get medical care.
Less than two weeks after the botched operation, a second set of organs was located — amazingly fast in comparison to the three years Jesica spent on a waiting list before her first operation. Eighty percent of patients awaiting transplants die before organs can be found.
Dr. Karen Frush, the hospital's medical director of children's services, said there was no sure way to tell when the brain damage occurred. But Mack Mahoney, a family friend and Jesica's chief benefactor, said doctors told the family it was due to the time Jesica was connected to life support.
"Life support ruins kidneys, it ruins brains, it ruins all the organs of the body," he said.
CBS News correspondent Mark Strassman reports that, under North Carolina law, the hospital didn't need the family's permission to take Jessica off life support, but the stage may be set for a potential legal tussle.
The Santillan family declined to donate any organs from Jesica's body, Puff said.
Jesica's place on the transplant list was determined by several factors, including the severity of her illness and her age.
Her immigration status played no role because hospitals may place non-U.S. citizens on their waiting lists and must give them the same priority as citizens, said Anne Paschke, spokeswoman for the organ network. But they cannot perform more than 5 percent of their transplants on non-citizens.
Heart and lung transplants are rare for teenagers: In the first 11 months of 2002, there were four nationwide for children between the ages of 11 and 17, UNOS' records show. The previous year, there were four.