Ophir Pines-Paz has held two major Israeli government positions, in which he served both as a portfolio minister and as a member of the cabinet. From 2005 to 2006, as part of the Ariel Sharon government, Pines-Paz served as the Minister of the Interior. During 2006, as part of the Ehud Olmert government, he served as the Minister of Science, Culture, and Sport and was a member of the Foreign Affairs and Defense cabinet. Following the 2006 Lebanon War quit the Ehud Olmert government and turned to focus his energy on the Knesset floor.

Jointly with his ministerial positions, Pines-Paz has been a member of Knesset (Israel's unicameral parliament) since 1996, when he was elected as a representative on behalf the Israeli Labour Party at the age of 34, until 2010. Pines-Paz served consecutively as part of the Labour faction in the 14th, 15th, 16th 17th and 18th (current) Knesset sessions. On January 10, 2010 Pines-Paz resigned from the Knesset.

Pines-Paz was the head of the Environmental Lobby in the Knesset. He was the chairman of the Interior & Environment Committee, responsible for issues such as local government, citizenship, policing, religious affairs and environmental protection. Pines-Paz also chaired the Constitution, Law & Justice Committee and has founded and chaired the Committee on Foreign Workers. Additionally, Pines-Paz has served as a member in various Knesset committees including the Foreign Affairs & Defense Committee, Immigration & Absorption Committee and the State Control Committee. Pines-Paz held several political offices: from 1999 to 2001, during the Ehud Barak administration, he served as the chairman of the parliamentary ruling coalition and as the chairman of the One Israel (Labour) Faction. From 2001 to 2003 he served as the General Secretary of Labour Party.

During the internal Labour primaries for ministerial positions in 2004, Pines-Paz received the highest number of votes and came in first place. During the last two internal Labor primaries for the Knesset (2007 and 2009) MK Pines-Paz came in second, and was placed third on the Labor Party list. Pines-Paz also came in fourth during the first round of the 2008 primaries for the position of party chairman (leader).

Pines-Paz was awarded as "Knights of Quality Government" (The executive authority) by The Movement of Quality Government. MK Pines-Paz was a recipient of the 2006 “Ometz” award given by "Citizens for Good Governance and Social Justice", and a recipient of the 1997 “Amitai” award for honest management and integrity.

Before entering the Knesset in 1996, Pines-Paz served voluntarily as the chairman of the Government Authority for Rehabilitation of Prisoners (1992-1996).

Between the years 1984-1993 Pines-Paz worked for the Jewish Agency. He was nominated at the age of 26 as a Deputy Director General for Immigration and Absorption department. Those were very exiting years of the "Moses Operation" and the "Salomon Operation" from Ethiopia and the mass immigration from the former Soviet Union.