The pan-African trial in 6,000 children aged five to 17 months found the vaccine reduced the numbers infected with the most serious form of malaria by 56 per cent, in the 12 months after vaccination, compared to those who did not receive the jab.
It also reduced the number of severe malaria cases by 47 per cent.
As little as a decade ago vaccine experts considered the challenge of tackling the mosquito-borne infection impossible.
But scientists on the project said the results proved that “innovation and a lot of hard work” paid off in the end.
The vaccine, RTS,S, is a collaboration between GSK, the drugs giant; the Bill and Melinda Gates Foundation, the PATH Malaria Vaccine Initiative and individual African research centres.
Dr Chris Elias, chief executive officer of PATH, said: “Today, in the face of a seemingly intractable challenge, resignation is moving aside in favour of hope and possibility. We are on track to make history with this vaccine trial.”
GSK has invested some $300 million (£191m) in the project, which it does not intend to recoup, and Bill Gates $200 million (£127 million). The drugs firm intends to make the vaccine as cheaply as possible, supplying it at cost price plus five per cent mark-up, which it has pledged to re-invest in research and development for underfunded vaccines.
Malaria affects vast swathes of the tropics and sub-tropics. About 225 million people are infected every year, while some 800,000 die – mostly children in sub-Saharan Africa.
The results of the phase three trial were published on Tuesday in the New England Journal of Medicine.
According to the researchers, led by Dr Tsiri Agbenyega who chairs the RTS,S Clinical Trials Partnership Committee, the initial results show the vaccine “has the potential to have an important impact on the burden of malaria in young African children”.
Results from the same trial, of vaccinations in six-to-12-week old babies, will be reported in a year. These are crucial because doctors want to incorporate the vaccine in the immunisation schedule many countries have for babies, for diseases such as measles and polio.
After that, follow up data for three-years post-vaccination will need to be examined, to see if it has long-lived protection.
The scientists hope that the vaccine will be ready for roll-out by 2015.
Mr Gates said: “A vaccine is the simplest, most cost-effective way to save lives. These results demonstrate the power of working with partners to create a malaria vaccine that has the potential to protect millions of children from this devastating disease.”