McKenzie replaced Fiona Nash as deputy leader of the Nationals during the 2017 parliamentary eligibility crisis, and as a result was elevated to cabinet.

McKenzie resigned from cabinet and as deputy leader in 2020 as a result of a scandal surrounding the administration of community sporting grants.

She was elected deputy leader to Barnaby Joyce in December 2017, replacing Fiona Nash after her disqualification from parliament due to dual citizenship.

[10] McKenzie's gay younger brother confronted her on her views in a letter to the Bendigo Advertiser and on the panel discussion program Q&A.

[11][12] In May 2024, McKenzie called Fatima Payman's comments "Absolutely appalling" during which Payman accusing Israel of genocide during Israel-Hamas war and using phrase "From the river to the sea Palestine will be free, and asked "What’s the Prime Minister going to do with this Senator who has completely been subordinate to him?”[13] As Agriculture Minister McKenzie was instrumental in protecting Australia's pork industry from African Swine Fever.

On 11 December 2019 McKenzie announced $66.6 million [14][15][16] to boost Australia's defences against the virus which has a high mortality rates in domestic pigs.

McKenzie said the Bill sent a clear message that animal activists who use the personal information of farmers to incite trespass risked jail.

[31] In January 2020, McKenzie was widely accused of pork-barrelling[32][33][34][35] after the release of a report by the Commonwealth auditor-general which found that a $100 million sports grant program she oversaw in the lead-up to the 2019 Australian federal election was administered in a way that "was not informed by an appropriate assessment process and sound advice".

One Adelaide rugby union club was awarded a $500,000 grant under the scheme for new female change rooms, despite not fielding a women's team since 2018 when it was embroiled in a sexism controversy.

[52] Following the revelation that McKenzie awarded a $36,000 grant to a regional Victorian shooting club without declaring that she was a member, on 22 January 2020 Morrison referred the report of the Commonwealth Auditor-General to the Secretary of the Department of the Prime Minister and Cabinet for advice in relation to the conduct of ministerial standards.

[60] In an interview with ABC reporter Annabel Crabb, McKenzie specifically identified Prime Minister Morrison’s treatment of Australia Post CEO Christine Holgate as a pivotal moment in the former Coalition Government’s election loss.

[61] In McKenzie’s view, the pressure Morrison applied to Holgate to induce her to step down in the wake of critical media reports fatally damaged the perception of the Coalition amongst professional and, even, conservative women.

McKenzie has been actively working to repair this relationship as part of a strategy to return the Coalition to power at the next federal election.

[62] McKenzie became Chair of the Select Committee on Commonwealth Bilateral Air Service Agreements (popularly referred to as the Qantas Inquiry) on 5 September 2023.

[63] The Senate established this inquiry in the wake of Labor Transport Minister Catherine King’s decision to decline Qatar Airways’ request for additional capacity into Australia.

This decision prompted significant consternation in sections of the Australian electorate[64][65][66] due to elevated airfare prices,[67][68] particularly on the high demand Europe route,[69] in the wake of the COVID-19 pandemic.

Although the move rankled Indi-based Liberal Party members, McKenzie had planned to relocate to North East Victoria for many years and was waiting for Department of Finance approval.

[80][81] In January 2021, it was reported that McKenzie was in a relationship with Simon Benson, the national affairs editor for News Corp Australia.

It was launched by journalist Paul Kelly, who described it as "highly readable",[83] while historian Ross Fitzgerald reviewed it as "a helpful reintroduction to John McEwen", but "somewhat of a hagiography" and less complete than a previous full-length biography.