Costello decided in 2009 not to seek another term of office at the next federal election. On 17 September 2009, O'Dwyer was pre-selected to stand as the Liberal Party candidate for Higgins at the next election. Peter Costello then announced his resignation from Parliament in October 2009. He stated that he chose to retire ahead of the next federal election as a contribution to renewal of the Liberal Party and that O'Dwyer would contribute to this process. A by-election was held on 5 December 2009. O'Dwyer was considered a "shoo-in", especially since the Labor Party did not contest the seat. In winning preselection, O'Dwyer became the first woman to win Liberal Party preselection for a safe seat in metropolitan Melbourne. During the preselection process federal Liberal politicians Sophie Mirabella, Fran Bailey and Helen Coonan claimed that there had been a sexist campaign against O'Dwyer's candidacy, with some preselectors being told that a "leadership seat" such as Higgins was unsuited to a woman and that being elected to a federal seat might endanger her marriage.
At the 2016 federal election, O'Dwyer was re-elected with a two-candidate preferred vote of 57.99% and a 52.5% primary vote. A Greens-funded Lonergan seat-level opinion poll conducted from a sample of 1,100 voters in Higgins took place a month out from the 2016 election on 3−4 June. It suggested the Liberal primary vote may have decreased substantially. However, the poll proved inaccurate, with O'Dwyer winning comfortably.
Minister
O'Dwyer had been serving as Parliamentary Secretary to the Treasurer in the Abbott Government from December 2014, until the leadership spill of the Liberal Party occurred in September 2015. Malcolm Turnbull won the spill and was sworn in as Prime Minister on 15 September 2015. Turnbull introduced an overhaul of the cabinet, which saw O'Dwyer appointed to Cabinet as Minister for Small Business and Assistant Treasurer in the First Turnbull Ministry. Following the re-election of the Turnbull Government in 2016, the O'Dwyer was appointed as the Minister for Revenue and Financial Services, a name change. O'Dwyer was assigned two additional responsibilities, as the Minister for Women and the Minister Assisting the Prime Minister for the Public Service, in December 2017. Following the commencement of the Morrison Government, O'Dwyer became the Minister for Jobs and Industrial Relations, in addition to her ongoing role as Minister for Women. In 2018 O'Dwyer was listed as one of BBC's 100 Women. On 19 January 2019, O'Dwyer announced that she would not be contesting the upcoming election as her two children would be approaching primary school age and she wanted to give her and her husband the best opportunity for a third child.
Personal life
She is married to Jon Mant, a business executive, and has two sisters and one brother. Her daughter, Olivia, was born in 2015. On 13 April 2017, O'Dwyer gave birth to her second child Edward, making her the first Cabinet Minister to give birth while in office.