Harrison was dubbed "the man with the golden arm" for having unique properties associated with his blood plasma.
" I wish it's a document that someone breaks, due to the fact that it will certainly indicate they are devoted to the reason", Mr Harrison stated of his last contribution.
Despite once being quoted as saying that he had no plans to stop donating blood, Harrison made his 1,173rd - and last - donation on Friday, at a point where he had already exceeded Australia's age limit for blood donors.
Jemma Falkenmire, spokesperson for the Blood Service, said: "Every bag of blood is precious, but James' blood is particularly extraordinary".
'Medications like Anti-D are a life-giving intervention for thousands of Australian mums, but they are only available because men like James give blood'. If left untreated, the baby can suffer brain damage or die.
As recalled by the Washington Post, Harrison chose to become a blood donor when he was 14-years-old, after he survived a chest operation that required the removal of one of his lungs, keeping him in the hospital for three months.
James Harrison has donated his blood, almost every week, since the past 60 years.
Using plasma extracted from Harrison's blood, doctors devised the Anti-D injection, which was first given in 1967 to a pregnant woman at Australia's Royal Prince Alfred Hospital.
The blood becomes sensitized when the positive RHD blood is exposed to the negative blood and causes the mother's immune system to produce molecules that will fight the infection, called antibodies, that will destroy the cells.
During pregnancy, if a mother has Rh- blood and her fetus has Rh+ blood, it can cause problems if their blood starts to mix.
The antibodies can continue attacking the baby's red blood cells for a few months after birth.
She continued: "Australia owes a big thank you to James Harrison". The disease however does not harm the mother.