He has held several other previous public positions which include that of the magistrate and the chairman Electricity Regulatory Board.

Wetangula actively participated in organisation of funds-drives to set up projects on self-help basis and has been offering legal services to the local people.

He was appointed into the cabinet by President Mwai Kibaki on 8 January 2008, amid Kenyan crisis, 2007-2008 regarding the results of the concurrent presidential election, Wetangula was named Minister for Foreign Affairs.

[2] After a power-sharing agreement was reached between Kibaki and Raila Odinga, both of whom claimed victory in the presidential election, Wetangula retained his post in the Grand Coalition Cabinet named on 13 April 2008.

This is because Raila Odinga was unhappy with the fact that his fellow luo was not in that position and therefore instructed that Orengo should replace Wetangula.

Raila Odinga became a casualty after losing the presidential contest in 2022 general election, as Wetang'ula made William Ruto the fifth President of Kenya.

[6] Wetangula stepped down as Minister for Foreign Affairs on 27 October 2010 due to an investigation on his alleged involvement in the Kenyan Tokyo embassy scandal.

The Bungoma High Court nullified his election on 30 September 2013 and the Speaker of the Senate declared the seat vacant on 16 October 2013.

Wetangula retained his Bungoma senate seat in the August 2022 Kenyan general election, winning by a landslide.

On 8 September 2022, he contested successfully to become the speaker of the 13th Parliament of Kenya after defeating his only competitor Kenneth Marende.