In 2004, he won election to the executive council of UMNO's youth wing, by garnering the highest number of votes of any candidate. He was also seen as a potential candidate for being the deputy chief of UMNO Youth, but he later withdrew his candidacy.
Mukhriz was noted for his continuous efforts in speaking for his father in the events of the rift between Prime Minister Tun Abdullah Ahmad Badawi and his father. In 2006, his father lost a bid to be elected as one of seven delegates from Kubang Pasu to UMNO's general assembly; Mukhriz was elected as one of the seven. Mukhriz drew flak from sections of UMNO after he commented on Prime Minister Abdullah's speech at the assembly that he was a "little bit" disappointed and that it had offered nothing new. He later apologised for his remarks.
In the 2008 Malaysian general election, Mukhriz won the Jerlun Parliament Seat with the sum of the DUN differing markedly from Parlimen. Before this, he offered himself to contest in Langkawi Parliament Seat but was rejected by 85 out of 91 UMNO branches in Langkawi. However, many Langkawi leaders backed him later. The Jerlun UMNO division welcomed Mukhriz to contest in their Parliament seat and promised to give him full support in the election.
In 2009, Mukhriz contested as a candidate for the new UMNO Youth Chief after the wing's predecessor, Datuk Seri Hishamuddin Hussein released his position. He was rivalled by Khairy Jamaluddin and Khir Toyo. Nominations for the posts coincided with division meetings which took place between October and November 2008. Mukhriz was initially seen as leading in nominations compared to Khairy but eventually lost in the final vote count.
However, a controversy was sparked when Khairy was allowed to contest for the post even though he was found guilty for being involved with money politics by the UMNO Disciplinary Board, while others who were found guilty for the same offence, such as Mohd Ali Rustam who was supposed to contest for the UMNO Vice-President post, were not allowed to contest for their respective posts. However, Khairy denied the allegation, as stated in his blog.
In the 2013 election, Mukhriz gave up his seat in federal parliament to contest the Kedah State Assembly seat of Ayer Hitam. The move was taken with a view to becoming the Chief Minister of Kedah if the Barisan Nasional coalition could defeat the Pakatan Rakyat state government led by Azizan Abdul Razak. Mukhriz won Ayer Hitam (defeating the Pan-Malaysian Islamic Party (PAS) incumbent), Barisan Nasional reclaimed the state government, and Mukhriz was sworn in as Chief Minister on 6 May, the day after the election, in the presence of his father.
On 21 June 2013 Mukhriz attempted to charge Penang for the use of water from a river located in Penang state, on the basis that the source of the water was in Kedah. In return the Chief Minister for Penang, Lim Guan Eng, requested the Kedah government to pay rent for the land which the river occupies in Penang state.
In January 2016, UMNO Kedah leaders, led by Ahmad Bashah Md Hanipah, declare the loss of confidence towards Mukhriz due to "his inability to maintain a united party leadership". The move is widely believed to be a reprisal orchestrated by the Prime Minister Najib Razak's camp in UMNO, which was increasingly infuriated by Mahathir's and Mukhriz's criticisms against Najib. He resigned on 3 February 2016 after losing the majority of support among the assemblymen. Ahmad Bashah, who is also the Bakar Bata assemblyman, succeeded him as the 12th Chief Minister of Kedah.
He went to the Sophia University, Tokyo in 1982, where he received a bachelor's degree in business management. He later received another bachelor's degree in marketing after graduating from Boston University in 1987.
Mukhriz has held various posts in several business firms, which include Opcom Holdings, Kosmo Tech as well as the Malaysian Franchise Association. He is also the executive director of Perdana Peace Global Organisation.
Mukhriz is married to Datin Paduka Norzieta Zakaria on 14 November 1993, and has four children. He is currently serving as Chairman of the Board of Directors of Malaysian cancer vaccine company, Bioven.