In September 2019, after Amber Rudd resigned from Johnson's cabinet, Coffey was appointed as Secretary of State for Work and Pensions.

After Truss resigned in October 2022, Coffey was appointed by Rishi Sunak as Secretary of State for Environment, Food and Rural Affairs.

After resigning in November 2023, Coffey lost her seat in Parliament at the 2024 general election[5] but was appointed the House of Lords later that year.

[9][10] However, in 1991 she was asked to withdraw having obtained poor college examination results twice allegedly due to spending too much time on extra curricular activities including rowing and politics.

[17] The Conservative Party won 35.2% of the vote, giving it four seats, but Coffey was seventh on the list in this proportional representation system, and was not elected.

[32] After serving as a member of the Culture, Media and Sport Committee from July 2010 to October 2012, Coffey was appointed Parliamentary Private Secretary to Michael Fallon, Minister for Business and Energy.

[33] Coffey faced criticism in 2011 from some Suffolk residents over her support for the government's proposal to sell off forestry and woodland in public ownership.

Protesters argued that "experience shows us that when private landowners come in they close car parks and make access as difficult as possible".

[51] In September 2021, Coffey was accused by opponents of miscalculating the amount of work a Universal Credit claimant would need to do in order to make up for the proposed end of the £20-a-week increase in benefits, brought in to assist people during the COVID-19 pandemic.

In January 2022, Coffey tweeted support for prime minister Boris Johnson in regard to Partygate allegations, stating that she considered his apology to be sincere.

[56] Coffey continued to defend Johnson in July 2022 when he was accused of overlooking MP Chris Pincher's alleged sexual misconduct when he was appointed Deputy Chief Whip.

[10] Truss appointed Coffey as Deputy Prime Minister and Health and Social Care Secretary in her new government on 6 September 2022.

[59] Asked about nurses leaving to go abroad, Coffey said: "It is their choice of course if they want to do that, but then we also have an open route for people to come into this country who are professional staff".

[61] On 15 October 2022, it was reported Coffey was planning to allow people to obtain antibiotics from pharmacists without a prescription from a general practitioner, which led to criticism by medical experts due to it increasing the risk of antimicrobial resistance (AMR).

[74][75] Labour MP Rachael Maskell said, "It's very shocking that the Environment Secretary shifted blame for food poverty onto people because they are on low wages and are poor."

She signed an early day motion in 2011 set down by Labour Liverpool Walton MP Steve Rotheram requesting a knighthood for Kenny Dalglish.

[43] In an interview with The Sunday Times, Coffey said she spent a month in hospital in 2018 after the stress of being a government minister led to a brain abscess.

[86] On 4 July 2024, Coffey was appointed Dame Commander of the Order of the British Empire (DBE) in the 2024 Dissolution Honours for political and public service.