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.
Initial inquiries indicated 10 people had died, 11 were injured and taken to hospital via air and road ambulances, and a further 18 passengers were uninjured, police said in a statement.
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.
"He's been the driver of a motor vehicle collision where there have been fatal injuries and there will be charges pending," she said.
The driver was not seriously injured in the crash and was arrested at Cessnock Police Station after being released from hospital.
It's understood some of the injured passengers have been taken to Newcastle's John Hunter Hospital, while others have been flow on to Sydney.
Media reports say the bus had been returning from a wedding reception at Lovedale.
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.
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.
"We're still waiting for information to come to light around the cause of the crash, but what we do know is it's truly tragic circumstances where quite a lot of people have sadly lost their lives."
Prime Minister Anthony Albanese posted a message of sympathy on Twitter to the loved ones of those killed in what he called a horrific tragedy.
"For a day of joy to end in such devastating loss is cruel indeed," he said.
"Our thoughts are also with those who have been injured."
A senior NSW Ambulance officer told Seven News the magnitude of the accident had been confronting for first responders.
"Whilst they are paramedics every day of their lives, something like this is not a job that they go to every day," she said.
"I'm incredibly proud of all the paramedics that attended. They did a fantastic job under the circumstances and no doubt they will be reflecting and we will have the right support there for them."
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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