An analysis of DNA from 20 skeletons excavated from a suspected Great Plague burial pit at the Bedlam burial ground, at the New Churchyard, found a significant proportion of the samples tested positive for the yersina pestis bacterium.
This same bacterium, which causes the bubonic plague, was also the cause of the 1348 Black Death and an 1855 bubonic plague outbreak in China.
The Great Plague was the last known outbreak of bubonic plague in the UK. It claimed an estimated 100,000 lives and was almost a quarter of London's population at the time, before it was wiped out by the Great Fire of London in 1666 - which was commemorated in a 350-year anniversary event last week.
Researchers sent teeth from the skeletons to the Max Planck Institute for the Science of Human History in Germany.
Senior human osteologist at the Museum of London Archaeology, which helped organise the Bedlam excavation, told the BBC the teeth were "like an isolated time capsule", making them the best part of the skeleton's anatomy to hunt for evidence of the true cause of their deaths.
The findings put to rest the cause of the Plague after queries from scientists over recent years as to the true cause of the epidemic.