Van 't Wout served as a member of the House of Representatives from September 20, 2012 to 2 July 2020. In the 2012 parliamentary elections, he was in 27th place, and was elected lower. He received 1,178 preferential votes. In the 2017 House of Representatives elections, he was in 13th place and was elected again. Until 26 October 2017, he was spokesperson for Long-term care, Social Support Act and Social Affairs and Employment. From 26 October 2017 he was vice-chairman of the VVD and spokesperson for the Ministry of General Affairs.
In July 2020 Tamara van Ark was promoted from State Secretary of Social Affairs and Employment to Minister for Medical Care. Van 't Wout replaced her as State Secretary.
Minister of Economic Affairs, 2021
After the departure of Eric Wiebes, Van 't Wout was appointed as his successor as Minister of Economic Affairs and Climate Policy as of 20 January 2021 in the demissionarythird cabinet of Prime Minister Rutte. He was in 6th place on the VVD candidate list for the 2021 elections. On 31 March 2021, he was sworn in again as a member of parliament.
On 24 May 2021 it was reported that Van't Wout was suffering from a occupational burnout and would not be returning to the parliament for at least 3 months; fellow cabinet ministers Stef Blok and Sigrid Kaag took over and shared the economic affairs portfolio in his absence.[5][6]