Vara has been involved with the Conservative Party since the late 1980s and has held various posts at local, regional and national levels. As Vice-Chairman of the Party, he had a broad range of responsibilities. These included advising Michael Howard, deputising for the Party chairman, party spokesman with the media and looking after Conservative Future. Vara was elected Member of Parliament for North West Cambridgeshire in May 2005. He had previously contested the Birmingham Ladywood seat at the 1997 general election, which Labour's Clare Short won easily, and Northampton South in the 2001 general election, which Vara failed to win by only 885 votes. At the Conservative Party Conference in 2000, he was awarded the accolade of official "rising star" of the Party, with Lord Alexander of Weedon describing him as a "future Conservative Party leader". In the run up to the 2001 general election, Vara was a member of the Party's manifesto teams for Law and Order and Legal Affairs. On 30 June 2016, Vara confirmed his support for Michael Gove in the impending Conservative leadership contest. Vara said "I have worked very closely with Michael Gove at the Ministry of Justice and have been very impressed with him. He is a man of conviction with a very sharp intellect. He cares passionately about Britain and I believe he has the necessary qualities to lead our negotiations with the EU." In the 2019 Conservative leadership election he initially backed the utimately-aborted candidacy of Dominic Raab.
The Breast Cancer Bill was Vara's chosen issue after he was one of 20 MPs who were selected at random to introduce a private member's bill to the House of Commons in 2006. He has campaigned to broaden the age of routine breast cancer screening for women from the present 50–70 age group to 45–75 years. The proposal was not supported by the government, which Vara claimed effectively blocked its progress by talking through to the end of the debate. Vara has given his backing to Breast Cancer Campaign's award-winning national "wear it pink" day, and showed his support for breast cancer charity Breakthrough Breast Cancer at a meeting in the House of Commons.
Early on 15 November 2018, Vara announced his resignation as a Northern Ireland Minister on Twitter, posting his letter of resignation. His resignation followed the previous day's marathon-length cabinet meeting to discuss the draft Brexit withdrawal agreement. Vara was opposed to Brexit prior to the referendum on the UK's continued EU membership in June 2016. However, Vara resigned from his role at the Northern Ireland Office as he did not believe the Government's proposed exit agreement honoured the outcome of the referendum.
