Christened Boramy - meaning "full moon" in the Khmer language - because of her bulbous shape, the four-metre (13-foot) long female was released back into the river after being electronically tagged to allow scientists to monitor her movement and behaviour.
"This is very exciting news because it was the world's largest fish," said biologist Zeb Hogan, ex-host of the "Monster Fish" show on the National Geographic Channel and now part of a conservation project on the river.
"It is also exciting news because it means that this stretch of the Mekong is still healthy.... It is a sign of hope that these huge fish still live (here)."
Boramy, netted last week off Koh Preah, an island along the northern Cambodian stretch of the river, took the record from a 293 kg giant catfish that was caught upstream in northern Thailand in 2005.
The Mekong has the third-most diverse fish population in the world, according to its River Commission, though overfishing, pollution, saltwater intrusion and sediment depletion have caused stocks to plummet.
