Erdan worked as an advisor to Prime Minister Binyamin Netanyahu and was director of the Department for Public Petitions to the Prime Minister's office between 1996 and 1998. He also worked as an advisor to Likud MK Ariel Sharon in the 1990s.
Erdan was first elected to the Knesset in the 2003 elections. He retained his seat in the 2006 elections despite Likud's collapse from 40 to 12 seats, after winning fourth place on the list in the party's primaries. In the party primaries held on 8 December 2008, he won third place on the list, and was subsequently re-elected in 2009. He was appointed Minister of Environmental Protection, and the Minister in charge of coordinating between the Cabinet and the Knesset in the Netanyahu cabinet. Upon the government taking office in 2009, he expressed support for Avigdor Lieberman's speech opposing the Annapolis Conference and international pressure. He commented that "Israel does not take orders from Obama" and that "citizens of Israel have decided that they will not become the fifty first US state".
In the Knesset, Erdan has supported boosting ties between Israel and Evangelical Christians, as well as presenting bills to enforce no-smoking laws, permanently revoking the driving licenses of serial traffic offenders, and allowing the courts to revoke citizenship for "disloyalty to the state". Prior to submitting the latter bill, Erdan was involved in a spat with Israeli Arab MK Azmi Bishara. During a meeting of the Knesset Law and Constitution Committee to discuss a similar proposal by NRP MK Zevulun Orlev, Erdan interrupted a Bishara speech by shouting "Why don't you just go back to Syria?" in reference to Bishara's trip there the previous summer. Bishara responded by saying "Why don't you just go fuck yourself?" creating an uproar in the committee.
In 2011, Erdan turned down an offer to become Israeli ambassador to the United Nations citing his commitment to the environment and desire to further environmental reforms. In November 2014 he was appointed Minister of Internal Affairs following Gideon Sa'ar's resignation.
On 24 May 2015, Prime Minister Netanyahu appointed Erdan as Minister of Public Security, Strategic Affairs and Information. The Knesset confirmed him in a 58–55 vote the following day. Erdan's appointment came eleven days after he initially refused to join Netanyahu's new government as he deemed the Prime Minister's initial ministerial offers as insufficient. Two ministers, Yariv Levin and Ze'ev Elkin, surrendered their portfolios, and Minister without Portfolio Benny Begin resigned from the government in order to accommodate Erdan's appointment.
Outside the Knesset, Erdan is chairman of Al Sam, an organisation dealing with drug issues (he also serves on the Knesset's Committee on Drug Abuse), and also established the Lobby for Soldiers Missing in Action, of which he remains chairman. Erdan is also a member of the Israel Broadcasting Authority's General Assembly.