The 71-year-old is best known for his role in managing the COVID-19 crisis, fronting the media daily to inform about the virus and urge adherence to recommended health measures.
"As NSW Health Minister it has been the best of times and the worst of times," Hazzard said in a statement on Monday night, announcing his retirement from politics.
He said as health minister the best times were working with "incredibly talented medical and non-medical staff in our health system" and delivering 180 new hospitals and health facilities.
"The worst of times came with COVID-19. When the pandemic began, we were bracing for an expected 25,000 deaths in NSW in the first year," he said.
"There were many anguished nights. What followed was a gruelling and a deeply upsetting time where rapid decisions had to be made to try and keep 8.5 million people safe from the virus."
Mr Hazzard said he had decided it was time for a "new beginning".
He has represented the northern beaches seat of Wakehurst for 32 years, being elected first in 1991.
The former teacher and lawyer has been in cabinet since the Coalition's win in 2011, including as attorney-general and minister for planning, justice, social housing, community services and health.
NSW Premier Dominic Perrottet described Hazzard as a "tireless and committed advocate for people right across our state".
"Our state is a better place thanks to Brad's significant contribution," he said.
Mr Hazzard also highlighted the decriminalisation of abortion in 2019 as one of his proudest achievements.
"Working with colleagues across the political divide to right the antiquated wrong of potential criminalisation of women and doctors who found themselves making the difficult decision to undertake an abortion, was another important moment for me," he said.
