A bill which bans the sport and appoints an administrator to wind up the industry passed the Legislative Assembly early on Wednesday morning after several weeks of intense public debate.

The move by the Baird government follows the report of a special commission of inquiry which found up to 68,000 greyhounds were slaughtered as "wastage" in the past 12 years "because they were considered too slow to pay their way or were unsuitable for racing"

It recommended the NSW Parliament decide whether the industry has lost its social licence and should be no longer able to operate.

Several Nationals MPs have broken ranks to publicly oppose the ban, warning it will devastate local communities.

Opposition leader Luke Foley spoke for more than two hours against the shutdown. 

Three Nationals MP - Barwon MP Kevin Humphries, Cootamundra MP Katrina Hodgkinson and Clarence MP Chris Gulaptis - crossed the floor to vote against the bill, which was supported by 48 votes to 35.  

Former Liberal MP for East Hills Glenn Brookes, who currently sits on the cross bench as an independent after a staff member was charged with electoral fraud, also voted against the bill.

Debate ended shortly after 3.40am, with the bill passing by 49 votes to 30 on its third reading after amendments were considered.

"I am pleased the Parliament has strongly supported the Government's decision, because it is the right one, even though it has been a difficult one," said Premier Mike Baird.

"The bill is the direct consequence of the Special Commission, which found compelling evidence of systemic animal cruelty in greyhound racing and concluded there was a culture of cover-up that gave no comfort to those who hoped it could be reformed."

But Mr Foley said Mr Baird "is breaking the hearts of thousands of good men and women across the state."

"Let's throw the book at the bad people in the industry with life bans and prison sentences for those found guilty of animal cruelty but let's not destroy an entire industry and way of life," he said.

"Regional and rural NSW has been let down by a National Party which has done little more than act as a lickspittle for a North Shore Liberal Premier.

"There are thousands of good and honest people in the greyhound industry that will have their livelihoods destroyed by this Liberal-National Government."