Local media reports said the bus tipped over and quoted passengers as saying it was full and traveling very fast.
Police said they are investigating and arrested the driver on dangerous driving charges.
The crash left 15 men and four women dead and sent more than 60 others to a hospital.
Photos and videos published by local media or posted on social media showed the bus lying on its side while emergency workers treat injured passengers.
TV channels broadcast footage of rescuers cutting open the roof of the bus, operated by the Kowloon Motor Bus Co., and bodies of passengers laid out on the ground, covered in white sheets.
Multiple passengers interviewed by the TVB and Cable TV news channels said the bus was speeding. The passengers were not identified by name.
The South China Morning Post newspaper said it was the Asian financial center’s deadliest traffic accident since a 2003 bus crash killed 21 people.