The vehicle left a 30m skid mark on the road before toppling onto its side, tearing off parts of the roof.
As of 7.45pm, police said two people were still trapped in the bus. Ten were fighting for their lives in hospital while 15 were in a serious condition.
The bus was carrying a lot of passengers when it overturned on a highway in the suburbs. And then it was like the tyres slipped and the bus turned.
The safety of Hong Kong's waterways has also remained under scrutiny since 39 people were killed when a high-speed ferry and a pleasure boat crashed in 2012.
Police are investigating the cause of the accident. It was really chaotic on the bus.
"(The driver was) intentionally using the bus to throw a tantrum", another injured passenger told the Oriental Daily.More news: Police officer fatally shot in suburban Dallas apartment complex
While bodies of dead passengers were laid out on the ground, covered in white sheets.
Photographs of the incident show the bus on its side with the roof torn off.
Most of the passengers were horse racing fans, as the bus was travelling on a special route for horse racing days.
A representative for the Kowloon Motor Bus Co, the bus operator, said it would launch its own investigation into the crash and family members of the victims would get financial assistance.
Saturday's crash appears to be the worst since a double-decker bus fell off an elevated roadway in 2003, killing 21 people.
The fire brigade responded at 6:15pm.