Up to 50,000 people may have been buried at the site in Charterhouse Square in Farringdon if it proves to be the location of a plague cemetery mentioned in ancient records.
The records refer to a burial ground in the Farringdon area that opened during the Black Death in 1348.
Over the past two weeks, the archaeologists have uncovered 13 skeletons in two carefully laid out rows 2.5 metres below the road that surrounds the gardens in Charterhouse Square.
"The depth of burials, the pottery found with the skeletons and the way the skeletons have been set out all point towards this being part of the 14th century emergency burial ground," said Jay Carver, Crossrail's lead archaeologist.
"This is a highly significant discovery and at the moment we are left with many questions that we hope to answer," he said.
"We will be undertaking scientific tests on the skeletons over the coming months to establish their cause of death, whether they were plague victims from the 14th century or later London residents, how old they were and perhaps evidence of who they were," Carver added.
The skeletons are being carefully excavated and taken to the Museum of London Archaeology for laboratory testing.
The scientists are hoping to map the DNA signature of the plague which could help uncover the cause of the Black Death.
The bones may also be radio carbon-dated to try and establish the burial dates.
These are not the first skeletons found on the Crossrail project, with archaeologists already having uncovered more than 300 at the New Cemetery near the site of the Bedlam Hospital at Liverpool Street from the 1500s to 1700s.
The Crossrail line, under construction since 2009 and due to carry its first passengers in 2017, will run across London on an east-west route.
It will be mostly overground but is going underground in the centre of the city.
Discovery News. 2013. “Black Death Skeletons Unearthed by Crossrail Workers”. Discovery News. Posted: March 15, 2013. Available online: http://news.discovery.com/history/archaeology/black-death-skeletons-130315.htm