The plight of many lion populations is so bleak that fencing them in - and fencing humans out - may be their only hope for survival, said the report published in the journal Ecology Letters.
It is estimated that fewer than 30,000 lions remain in Africa in just 25 per cent of the species' original natural habitat today.
The study led by the University of Minnesota's Professor Craig Packer and co-authored by a large team of lion biologists used field data from 11 African countries.
The report found that conservation costs are lower, and lion population sizes and densities are greater, in reserves secured by wildlife-proof fences, compared to unfenced ecosystems.
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Lions in unfenced reserves were subject to a higher degree of threats from human communities, including retaliatory killing by herders, habitat loss and fragmentation, and overhunting of lion prey.
"These findings highlight the severity of the lion conservation crisis today and the limited choices we have to ensure a future for the species," said Dr Luke Hunter, President Panthera, a US-based wild cat conservation organisation.
Whether fencing or some alternative physical boundary such as intensely managed buffer zones, it is clear that separating lion and human populations will be essential for the species' survival, researchers said.
"We have shown that it is possible to keep both humans and lions in African landscapes by reducing lion-human conflict, but it requires extensive resources. As the numbers of people and their livestock continue to grow in Africa, it is essential to scale up these programmes to avert losing many lion populations," Panthera's Dr Guy Balme said.