[12] She was described as being part of Micheál Martin's effort to recruit young, progressive politicians and change the elderly, male-dominated image of Fianna Fáil.

[12] She was credited with spearheading the revival of Fianna Fáil in the Castlebar area after the 2012 Mahon Tribunal report had discredited former minister Pádraig Flynn.

On the tenth count, she won the fourth seat in the constituency, after Fine Gael's Enda Kenny and Michael Ring and Fianna Fáil's Dara Calleary.

[13][14] Appointed spokesperson on Defence in the Fianna Fáil Front Bench on 18 May 2016, she succeeded Seán Ó Fearghaíl, who had been elected Ceann Comhairle of the 32nd Dáil.

She failed to win re-election to the Dáil at the 2020 general election, losing a battle for the fourth seat in her constituency to Fine Gael's Alan Dillon.

[16][11] Speaking on Sean O'Rourke's Two Tribes podcast, she attributed the outcome to her support for repealing the Eighth Amendment "in what is predominantly a conservative constituency, particularly among Fianna Fail voters".

[24] However, at a Fianna Fáil selection convention on 5 February 2024—a three-way contest among Chambers, Laois–Offaly TD Barry Cowen, and senator Niall Blaney from Donegal—she was eliminated on the first count.

[26] Running three candidates in the constituency was described as a "surprise move", given that Fianna Fáil had not had an MEP there since Pat "the Cope" Gallagher lost his seat at the 2014 European Parliament election.

[27] However, the Business Post called Chambers a "dimming star" within Fianna Fáil, following the loss of her Dáil seat and her poor showing at the selection convention.

It quoted a senior Fianna Fáil TD who said the party had added Chambers to the ticket only after Fine Gael incumbent MEP Maria Walsh had called its other candidates "male, pale and stale".

"[31][32] Chambers was criticised for claiming, during a 29 November 2018 Dáil debate on the Health (Regulation of Termination of Pregnancy) Bill 2018, that "Abortion regret is made up and it does not exist".

[45] However, with Jim O'Callaghan and Senator Eugene Murphy, she subsequently laid out concerns about the proposed legislation, including that young men could be stigmatised for life as a result of "foolish comments.

"[46] In May 2024, while Chambers was visiting a relative's home in a rural area near Castlebar, a man in his early 20s was discovered hiding in the bushes outside with his belt removed and several buttons on his trousers undone.

We send support and solidarity to Lisa Chambers.”[49] In April 2023, Chambers married her long-term partner, Fine Gael politician Jarlath Munnelly, a Mayo county councillor who is also a teacher and youth services coordinator.

[41] After giving birth during the early stages of the COVID-19 pandemic, Chambers criticised as "barbaric" the restrictions in maternity hospitals that had prevented women from having their partners present during labour and childbirth.