His ascension as NSW Liberal Party leader comes as the state prepares to reopen to fully vaccinated people on 11 October after more than 100 days of COVID-19 lockdown.
Mr Perrottet has indicated he remains committed to the timeframe for reopening, declaring there is "light at the end of the tunnel" for NSW "to bounce back stronger, safer and more successful than ever before".
"We want to get people back into work, get business open again, and that is the focus of our government," he said.
The leadership spill was forced following Gladys Berejiklian’s sudden resignation last Friday, amid an investigation from the state’s anti-corruption watchdog.
Mr Perrottet paid tribute to his predecessor, describing her "as an inspiring role model for many, especially women and migrant communities".
Minister for Western Sydney Stuart Ayres was elected deputy Liberal leader unopposed in the ballot, promising their leadership would focus on communities across the state.
"We have been through immense challenges whether it is the city, the coast, the suburbs or the bush, [we] will be focused on the people of New South Wales," Mr Ayres told reporters.
Mr Perrottet had announced a deal ahead of the vote for Mr Ayres to take on the role, with Environment Minister Matt Kean sworn in as Treasurer.
The 39-year-old has long been touted as a potential future premier of the state, rising quickly through the ranks to become a key figure of the NSW Liberal Party.
Mr Perrottet had become the state's treasurer and deputy leader of the party in 2017, after first entering state politics in 2011.
The devout Catholic is considered a right faction member and has not shied away expressing his conservative values in public discourse and his voting record in parliament.
"My religious views and my Christian faith is something I am incredibly proud of," Mr Perrottet told reporters on Tuesday.
"People right across our state, in the main, believe in freedom of religion and freedom of the opportunity to serve in public life regardless of what your ethnic background is or what your religious values are."
He also addressed his decision to vote against decriminalising abortion in 2019.
"The position I took on that was similar to the position that many people in the parliament took and that many people across our state hold," he said.
"I've always said on issues of that nature that come up - they're rare, but when they come up from time to time - our party will always have a conscience vote."
Mr Perrottet said he would support a similar conscience vote on the consideration of assisted dying laws in NSW.
"These are difficult, sensitive, and challenging issues," he said.
"My view has always been ... that we provide for conscience votes on those issues."
He also stressed LGBTQI communities should not be concerned about his leadership of the state.
"No, not at all. A fundamental premise of my values is respect and dignity for everyone," he said.
Mr Perrottet also becomes premier after the state government recently committed to reducing emissions by 50 per cent below 2005 levels by 2030.
He said he remained committed to the state's plan to reach net zero emissions by 2050, but also maintaining "fiscal conservatism" in its approach.
"Government should not measure success in the size of the spend," he said.
"They should measure success in the outcomes they provided to improve people's lives right across the board."
The NSW government has been hit by three high profile resignations since last week with Nationals leader and deputy premier John Barilaro and Transport Minister Andrew Constance also announcing their exit from state politics.
Their departure means the Coalition is facing three by-elections with its slim majority in the NSW Legislative Assembly making any potential loss of a seat significant.
Mr Perrottet said he would wait until later this year to announce a cabinet reshuffle but wanted this to be a "diverse" leadership team.
"More diversity leads to better government. And that's something I'll focus on," he said.
Mr Stokes told reporters Mr Perrottet would have his undivided loyalty and support, following the leadership ballot.
"Dom Perrottet will be a magnificent premier," he told reporters.