Thousands of nurses have hit streets across NSW to demand a pay rise, defying an order to call off the strike.

Nurses and midwives walked off the job on Tuesday morning for a 12-hour protest after demands for a 15 per cent wage increase were rebuffed.

Rallies were scheduled for 16 locations including Albury, Newcastle, Tamworth and outside the premier's Sydney electorate office, where a boisterous crowd accused Chris Minns of turning his back on emergency workers.

Speakers accused government figures of hollow praise when thanking them for their service throughout the COVID-19 pandemic, suggesting real gratitude would be shown through a pay rise and improvements to conditions.

Labor has offered a 10.5 per cent wage increase to all public-sector workers over three years, including a mandatory rise in superannuation payments.

Protesters at Mr Minns' office held signs including "F*** the praise, where's the raise?" and "You don't pay, we don't stay", while another accused Treasurer Daniel Mookhey of "counting his cash while we count the dead".

Mental health nurse Skye Romer, who attended the protest after a 10-hour night shift, summed up the frustration of many in attendance.

"I am tired, I'm burning out, I'm over it and it's time midwives and nurses in NSW are paid what we're worth," she said.

Another protester, a nurse named Jackie from Cumberland Hospital, said conditions were forcing workers to leave the industry "in droves".

"I want to leave, I could be paid more at Woolworths and without all the extra stress of nursing, but I love my job," she said.

The strike prompted warnings to keep ambulances and emergency departments clear of minor cases.

Skeleton staffing will be maintained but longer waits in emergency departments and planned surgery cancellations are expected.

The strike went ahead despite the NSW Industrial Relations Commission ordering the Nurses and Midwives' Association to call off the action.

The union's president, O'Bray Smith, said nurses and midwives cared about patients, "unlike this government".

"We don't take industrial action lightly and we've pledged to play our part to ensure the patients of NSW are safe," she said.

Mr Minns said the requested pay increase was unaffordable and the government's existing offer was fair.

"I have to tell taxpayers across the state, if we implemented a 15 per cent, one-year increase in salaries, it would cost $6.5 billion, that's more than we spend on the entire police force in one year," he told Sydney radio 2GB.

But the union is unhappy that provisions for extra health funding that helped power Labor to its 2023 election win could not be extended to better wages.

Advocates have also pointed to the higher pay on offer interstate as driving an exodus of frontline workers.

Labor was "refusing to fix the gender pay gap" and deliver the state's largest female-dominated workforce fair and reasonable pay, union general secretary Shaye Candish said.

Three-in-four NSW public health workers are women, with median salaries 3.2 per cent below their male counterparts.

The union said the pay rise could be covered through capturing $3 billion in lost commonwealth health funding.

The strikes come as Labor juggles multiple battles with unions over pay, having convinced many in 2023 to take a snap, one-year deal for a four per cent wage rise.

Mr Minns said giving the nurses a 15 per cent bump would deliver a queue of other workers demanding an identical raise, including police, corrections officers and paramedics.

Health Minister Ryan Park told a budget estimates hearing he would apologise to any patient who missed treatment due to the strike.

"I didn't say this was the path I wanted nurses and midwives to go down, I remained at the table," he said.