The small boat was overloaded and sank about 50 m (160 feet) from its destination in southeastern Kandal province after it began taking on water late Thursday, local police chief Am Thou told AFP.
"It's a sad accident," Am Thou said.
The victims were aged between 12 and 15, while two adult boat operators and two students were rescued, he added.
In a Facebook post, Prime Minister Hun Sen expressed his condolences and urged people to be cautious during heavy floods that have raised the level of the Mekong.
Boat accidents are common in the Southeast Asian nation, with people who live along the river reliant on the vessels for transport.
In 2009, an overloaded river ferry capsized in northeastern Cambodia, killing at least 17 passengers.