The virus, found buried 30m down in the frozen ground, poses no danger to humans or animals, but other viruses could be unleashed as the ground becomes exposed, scientists said.
"This is the first time we've seen a virus that's still infectious after this length of time," said Professor Jean-Michel Claverie, from the National Centre of Scientific Research (CNRS) at the University of Aix-Marseille in France.
The pathogen, called Pithovirus sibericum, belongs to a class of giant viruses that were discovered 10 years ago.
These are all so large that, unlike other viruses, they can be seen under a microscope. And this one, measuring 1.5 micrometres in length, is the biggest that has ever been found, 'BBC News' reported.
Scientists thawed the virus and it replicated in a culture in a petri dish. Tests showed that it attacks amoebas, which are single-celled organisms, but does not infect humans or other animals.
Researchers believe that other more deadly pathogens could be locked in Siberia's permafrost.
Since the 1970s, the permafrost has retreated and reduced in thickness, and climate change projections suggest it will decrease further, researchers said.
It has also become more accessible, and is being eyed for its natural resources.
Claverie warned that exposing the deep layers could expose new viral threats.
He said that ancient strains of the smallpox virus, which was declared eradicated 30 years ago, could pose a risk.
"If it is true that these viruses survive in the same way those amoeba viruses survive, then smallpox is not eradicated from the planet - only the surface," he said.
"By going deeper we may reactivate the possibility that smallpox could become again a disease of humans in modern times," he added.
However, it is not yet clear whether all viruses could become active again after being frozen for thousands or even millions of years.
The study is published in the Proceedings of the National Academy of Sciences (PNAS).