Scientists based across Asia, in the US and the UK examined the Y-chromosomes of more than 12,000 people from across Asia and found no traces of any ancient non-African influence.
"This result indicates that modern humans of African origin completely replaced earlier populations in East Asia," the researchers write in the journal Science.
The main alternative explanation of human origins - that modern humans are descended from separate populations which developed in different places - is known as multiregionalism.
"That's the real power of the analysis. There has been data before but here you're really sampling all of the extant diversity in Asia," he said.
Genetic markers Spencer Wells and his colleagues, led by Li Jin of Fudan University in Shanghai, spent months collecting DNA samples from a total of 163 different populations as diverse as Karakalpaks in central Asia, American Samoans and Nagas in India.
They tested the samples for a set of three markers associated with a mutation of the Y-chromosome known to have originated in Africa an estimated 44,000 years ago.
If they had found anyone without any of the markers, it would have indicated that the individual might not have been descended from Africans. But they did not, lending weight to the "Out of Africa" theory.
Only men have a Y-chromosome, and so the study looked only at the male line.
'Historical science' The researchers suggest that investigations of mitochondrial DNA, which is only passed down the female line, might add to the evidence.
Spencer Wells added: "This is historical science. We're limited to studying the diversity which is extant today and examining the pattern.
"It's a question of how many times you have to look at the pattern.
"This is another step down the road to completely debunking the myth of multiregionalism. It's difficult to say when the final nail goes in the coffin, but I think we're getting close," he said.