Petraglia, who was not involved in the study, said it had major implications for understanding the spread of modern humans and our interactions with the Neanderthals.
The researchers said they spent more than 30 years carefully sifting through layers of dirt inside the cave, which is 140 kilometres north of the French Mediterranean city of Marseille
They discovered hundreds of thousands of artifacts that they were able to attribute to either Neanderthals or modern humans. These included advanced stone tools known as "points" that were used by homo sapiens — our closest ancestors — to cut or scrape and as spear tips.
Similar tools from almost the exact same period have been found some 3,000 kilometres (nearly 1,900 miles) away, in present-day Lebanon, indicating that modern humans with a common culture may have travelled across the Mediterranean Sea, said Ludovic Slimak, one of the lead authors of the new study.
While the researchers found no evidence of cultural exchanges between the Neanderthals and modern humans who alternated in the cave, the rapid succession of occupants is in itself significant, they said. In one case, the cave changed hands in the space of about a year, said Slimak.
Katerina Harvati, a professor of paleoanthropology at the University of Tuebingen, Germany, who was not involved in the study, said the findings upend the idea that most of the European continent was the exclusive domain of Neanderthals until 45,000 years ago.
However homo sapiens' first venture into the region wasn't particularly successful, she noted.
"Mandrin modern humans seem to have only survived for a very brief period of time and were replaced again by Neanderthals for several millennia," she said.
Slimak, an archaeologist at the University of Toulouse, said the findings at Mandrin suggest the Rhone River may have been a key link between the Mediterranean coast and continental Europe.
"We are dealing with one of the most important natural migration corridors of all the ancient world," he said.
He and his colleagues expect to publish several further significant findings based on the mountain of data collected from the cave. Slimak said a steady supply of sand carried in by the local Mistral winds has helped preserve a rich trove of treasures that rivals other famous archaeological sites.
"Mandrin is like a kind of Neanderthalian Pompeii," he said.