The bus was carrying a 56-year-old groom and four members of his party on Mount View Road in the NSW Hunter Valley before the crash on Wednesday morning.
Emergency services were called to the scene about 10.30am, where it was reported a serious crash had occurred.
Police confirmed two people remain in serious conditions, including the groom who was flown to John Hunter Hospital.
The remaining four people were also taken to hospital with injuries, while the bus driver will undergo mandatory blood and alcohol testing.
NSW Police launched an investigation into the cause of the accident.
"The only information we have at the moment is that (the bus has) veered from the road," Superintendent Steve Laksa said.
"There has been some details provided in how that may have occurred, but that will be a matter for the crash investigation to examine."
The incident comes two years after the 2023 Hunter Valley bus crash, where 10 guests were killed and 25 others injured returning from a wedding.
Bus driver Brett Andrew Button was under the influence of prescription painkillers when he lost control of the vehicle on a roundabout.
He was jailed for more than two decades after his erratic driving was found to have caused the crash, but is now appealing the length of the sentence.
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