He joined the Liberal Party in the early 1990s, and in 1995 Dominello was elected as a councillor for the City of Ryde. While on Council, Dominello was chair of a number of committees including the development committee and had a significant involvement in the establishment of the Ryde Aquatic Leisure Centre and the development of the Macquarie Business Park. Dominello served two terms, but did not nominate for the 2004 local government elections, citing his desire to concentrate on his legal career, and subsequently let his Liberal membership lapse.
New South Wales politics
On 3 September 2008, Labor Deputy Premier John Watkins, who was also the local Member for Ryde, resigned from parliament, resulting in the need for a by-election. Dominello nominated for preselection and won, defeating Ryde Mayor Vic Tagg and several other local party members. On paper, Ryde was a safe Labor seat; Dominello needed a 10-percent swing to win it. However, it was located in territory that had historically been marginal at the federal level. Additionally, the by-election came at a very bad time for the government, whose polling numbers had rapidly tailed off only a year after winning a fourth term. Dominello went into the contest as the overwhelming favourite to win. He duly defeated Labor candidate Nicole Campbell in a landslide, receiving a swing of more than 25 points on the day of the by-election. The swing, at the time the largest a sitting NSW government had ever suffered, turned Ryde into a safe Liberal seat in one stroke. He was subsequently sworn as a member of the Legislative Assembly in on 25 October 2008. Dominello has spoken in Parliament about a number of local issues including the future of Ryde Hospital, the Homebush V8 Supercar race and the increase to the Parking Space Levy. Dominello won the seat in his own right at the 2011 state election, picking up a healthy swing of 12.7 points and increasing his vote to 75 percent, making Ryde the 10th-safest Liberal seat. Following the electoral victory of the O'Farrell government at that election, Dominello was appointed as the Minister for Citizenship, Communities and the Minister for Aboriginal Affairs. Due to the resignation of Barry O'Farrell as Premier, and the subsequent ministerial reshuffle by Mike Baird, the new Liberal Leader, in April 2014 in addition to his existing responsibilities as a minister, Dominello was appointed as the Minister for Veterans Affairs and the Assistant Minister for Education. Following the 2015 state election, Dominello was sworn in as the inaugural Minister for Innovation and Better Regulation in the second Baird government. In 2017 Dominello was appointed as the Minister for Finance, Services and Property in the first Berejiklian ministry. Following the 2019 state election, Dominello was sworn in as the Minister for Customer Service in the second Berejiklian ministry, with effect from 2 April 2019. In September 2018, Dominello broke an arm while arm-wrestling NSW Attorney-General Mark Speakman in an office.