When he started donating, his blood was deemed so special his life was insured for one million Australian dollars.
His generosity stems from a brush with death he experienced when he was a teenager, he says.
His blood has since led to the development of a vaccine called Anti-D.
Just after he started donating he was found to have the rare and life-saving antibody in his blood.
At the time, thousands of babies in Australia were dying each year of Rhesus disease. Other newborns suffered permanent brain damage because of the condition.
An incredibly unique antibody in Harrison's blood makes it a true lifesaver for babies who could be affected by rhesus disease.
The condition occurs during some pregnancies, when a woman who has rhesus-negative blood produces antibodies that destroy her babies' cells. This can happen when the baby inherits rhesus-positive blood from the father.
As the University of Rochester Medical Center points out, Rhesus disease can cause anemia and organ enlargement in babies, among many other complications. It can even be fatal.
James Harrison made his 1,000th blood donation in 2011, earning himself a Guinness World Record, officials said.
Doctors still aren't exactly sure why Harrison has this rare blood type but they think it might be from the transfusions he received when he was 14, after his lung surgery. He's one of no more than 50 people in Australia known to have the antibodies, according the Australian Red Cross blood service.
"I think James is irreplaceable for us," says Falkenmire.
"I don't think anyone will be able to do what he's done, but certainly we do need people to step into his shoes," she adds. "He will have to retire in the next couple years, and I guess for us the hope is there will be people who will donate, who will also ... have this antibody and become life savers in the same way he has, and all we can do is hope there will be people out there generous enough to do it, and selflessly in the way he's done."
