The 58-year-old bus driver was taken to hospital for mandatory testing and subsequently arrested with charges expected.
Emergency services were called to the crash site about 11.30pm on Sunday at a roundabout on Wine Country Drive near Greta after reports the coach had rolled.
A total of 10 people were confirmed dead while a further 25 were taken to hospital with varying injuries, police said in a statement.
The bus was returning guests from a wedding reception at Wandin Estate winery in Lovedale to their accommodation in Singleton, roughly 30 minutes away, police said.
It's understood some of the injured passengers have been taken to Newcastle's John Hunter Hospital, while at least two were flow on to Sydney.
Police Acting Assistant Commissioner Tracy Chapman said it appeared only one vehicle was involved in the crash and that there is "sufficient information" to charge the driver, who was not seriously injured and taken to Cessnock Police Station.
"He's been the driver of a motor vehicle collision where there have been fatal injuries and there will be charges pending," she said.
As of Monday morning the bus remained on its side and Ms Chapman said it was possible the death toll would increase if further people were found to be trapped under the bus or if those with injuries worsened.
An investigation into the crash has started, following a large-scale emergency response involving local police, rescue squad and highway patrol officers, ambulance paramedics, NSW Fire and Rescue, and the Rural Fire Service.
A crime scene has been established, which will be examined by specialist forensic police and the force's Crash Investigation Unit.
No children are believed to have been involved in the crash, according to Ms Chapman.
NSW Premier Chris Minns expressed his condolences to those impacted by the tragedy and said support was being provided.
"I know the whole community of NSW, and in particular the people of the Hunter, will be shocked and saddened to wake up to this news today," he said.
Prime Minister Anthony Albanese told reporters in Canberra for a day of joy in a beautiful place to end in such devastating loss is cruel and unfair.
"People hire a bus for weddings in order to keep their guests safe and that just adds to the unimaginable nature of this tragedy," Mr Albanese said.
"The mental scars of this will not go away.
"They are there forever and we need to make sure that when the spotlight leaves, the care doesn't, for people who have witnessed this and poor people who've experienced this tragedy first-hand."
Wandin Estate said it is providing support to guests who need it and wished to maintain the family's privacy.
"We are deeply saddened to hear of the bus crash overnight that has claimed the lives of some of our guests," the statement said.
Wineries in the area are popular with groups such as wedding parties and Cessnock City Council Mayor Jay Suvaal said chartering a bus is common.
"There will be many people from across the state and across the country that have visited our area and done the same, and I'm sure they'll be passing on their thoughts to all those involved," he said.
Wine Country Drive remains closed in both directions at Greta, west of Maitland.
Motorists are being advised they can divert around the closure via Bridge Street, Drinan Street, Clift Street and the New England Highway.
The northbound and southbound off-ramps from the Hunter Expressway to Wine Country Drive are also closed, although through lanes are not affected.
Due to the nature of the crash, the NSW Transport Management Centre says there is no forecast for how long the road will be closed.
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