William C Campbell, who was born in Ireland and has forged a long career in the US, joined Japanese scientist Satoshi Ōmura in being rewarded for discoveries that the Nobel judges said had "revolutionized the treatment of some of the most devastating parasitic diseases".
Tu was praised for her research concerning a novel therapy against malaria and became only the 12th female recipient of a Nobel medicine prize to date.
All three winners are in their eighties.
The judges explained that Ōmura's work analyzing soil samples in Japan alongside Campbell's subsequent research, led to the development of ivermectin, a drug which has helped radically lower the incidence of River Blindness and Lymphatic Filariasis, as well as showing efficacy against an expanding number of other parasitic diseases.
Meanwhile they revealed how Chinese scientist Tu had searched through ancient literature on herbal medicine as part of her efforts to find new leads for malaria treatments.
She carried out tests using an extract from the plant Artemisia annua and discovered that it could be effective, although her results were inconsistent. Eventually she managed to work out which component of the plant was able to kill Malaria parasites at an early stage of their development.
"These two discoveries have provided humankind with powerful new means to combat these debilitating diseases that affect hundreds of millions of people annually. The consequences in terms of improved human health and reduced suffering are immeasurable," said the Nobel Assembly in a press statement.
Winner Youyou Tu. Photo: TT/Yang Wumin/Xinhua via AP
Swedish newspaper Dagens Nyheter (DN) said on Sunday it believed the prize committees would this year be looking to even out the gender gap among laureates, the vast majority of whom have been men over the years.
But Juleen Zierath of the Karolinska Institute's Nobel Committee told The Local after the announcement that gender was not a deciding factor when selecting Tu or any of the the other winners: "Truly, truly we look at the nominations that come and we look at them for what they have done. What is the discovery? (...) And then what is the benefit for mankind. We can't pay attention to sex or religion or nationality."
She agreed, however, that it was good that the committee had selected a positive female role model for women in science for the medicine prize, adding: "I just hope she knows now!"
The committee said earlier it had struggled to get hold of Tu to share the news of her win. Usually its members ring scientists at home or at their offices, but this time it was "very hard" to source contact information, Zierath acknowledged.
Journalists in Stockholm were given a presentation about the winners. Photo: Fredrik Sandberg/TT
During a press conference following the announcements, some journalists questioned the theme for this years prizes, given that some parasites appear to be becoming resistant to drugs designed to tackle parasitic diseases.
Responding to the criticism, Zierath acknowledged that "down the line we can't predict what will happen".
But she told The Local: "In this case remember these drugs have been used for decades now and they have saved millions, really millions literally of lives (...) and that's why these winners have been recognized."
The Nobel prizes were created by Swedish philanthropist and scientist Alfred Nobel in his 1895 will, and were first handed out in 1901.
The medicine award was the first Nobel prize to be announced in 2015. The physics, chemistry and literature prizes are set to be revealed in Stockholm later this week, while the economics prize will be announced next Monday. The peace prize will be handed out in Oslo on Friday.