He served as a Member of the House of Representatives from 19 May 1998 until 24 March 2000, when he became State Secretary for Finance in the Cabinet Kok II following the resignation of Willem Vermeend who became Minister of Social Affairs and Employment. He returned to the House of Representatives on 23 May 2002, following the Dutch general election of 2002. The Labour Party suffered a landslide defeat in the election losing 23 seats, then Party leader Ad Melkert was blamed for the defeat and resigned. Bos announced his candidacy for the Labour Party leadership election and won by a landslide with 60% of the votes. Bos became the Labour Party party leader on 19 November 2002 and the Parliamentary leader of Labour Party in the House of Representatives on 19 November 2002 and became the lijsttrekker for the Dutch general election of 2003. The Labour Party was the largest winner of the election, gaining 19 seats (from 23 to 42) and became the second largest party in the House of Representatives. After a failed cabinet formation a new cabinet was formed without the Labour Party. Bos served as opposition leader during the parliamentary period of the Cabinets Balkenende II and III. For the Dutch general election of 2006 Bos again as lijsttrekker lost 9 seats but the Labour Party remained the second largest party with 33 seats. The following cabinet formation resulted in a coalition agreement which formed the Cabinet Balkenende IV, comprising the Christian Democratic Appeal (CDA), Labour Party (PvdA) and the ChristianUnion (CU). Bos became Minister of Finance and Deputy Prime Minister, the cabinet took office on 22 February 2007. The cabinet fell on 20 February 2010 as the result of disagreement between CDA and Labour Party over the extension of ISAF mission in Afghanistan. Bos resigned his position as Party leader to spend more time with his family and retired from active politics.
Since his retirement from politics, Bos became a partner at the professional services firm KPMG and is also a consultant for the financial sector. On 21 June 2013 Bos was appointed as chairman of the board of directors of VU University Medical Center.
Bos was raised in a Doorbraak social-democratic family with a Protestant background in Vlaardingen. His father founded the ecumenical development cooperation fund ICCO, which he also led for many years. Between 1969 and 1974 Bos attended the Protestant elementary school de Beurthonk in Odijk. From 1974 he attended the Protestant high school Christelijk Lyceum in Zeist. In 1980 he graduated specializing in sciences and classics. In 1980–81 he was a Voluntary Instructor at the YMCA National Centre in Curdridge in the United Kingdom.
He became a member of the PvdA in 1981. In the same year Bos started studying Political Science at the Vrije Universiteit in Amsterdam. In 1982 he also took up Economics. In 1988 he graduated cum laude in both subjects.
From 1988 till 1998 he worked for Royal Dutch Shell in various positions. With a background in Shell, he differs from other Dutch leftwing politicians, who rarely have a background in a major multinational corporation. Bos began to work for Shell because he thought that "the Dutch Left should not leave the business world to the Dutch Right".
Between 1988 and 1990 he worked at the Pernis Refinery as a management consultant, where he was a specialist on training and reorganisation. In 1990 he became policy advisor for the central board, specializing in labour relations and working conditions, he also served as representative of the central board in its dealings with the central works council. In 1992–93 he was stationed as general affairs manager for Shell Romania Exploration, where he was responsible for setting up the Romanian branch of Shell. In 1993 he was stationed in Hong Kong, to work as staff planning and development manager for Shell Companies in Greater China, responsible for the recruitment and selection of new manager for Shell in South Korea, Taiwan, Hong Kong and China. In 1996 he returned to Europe, and worked as a consultant for new markets for Shell International Oil Products in London, focusing on acquisition in developing LPG markets in South America and Asia. In 1998 he left Shell to enter Dutch politics. For a short while he was policy advisor for the PvdA parliamentary party in the lower house and a personal assistant of the party's financial spokesperson, Rick van der Ploeg.
In 1998 he was elected into the lower house of parliament for the PvdA as finance specialist. He campaigned together with Rick van der Ploeg and Willem Vermeend as "the Polderboys" and gave lectures in economics at universities. In 2000, due to a cabinet reshuffle, he succeeded Willem Vermeend as staatssecretaris for Finance, and became responsible for taxation, monetary policy and finances of lower-level government. Together with Finance Minister Gerrit Zalm he was able to get parliamentary support for a radical reform of the tax system. After the May 2002 elections he returned to parliament, as a specialist on income policy and health affairs.
After the fall of the first Balkenende cabinet Bos was elected top candidate for the following elections and de facto leader of the PvdA in the 2002 PvdA leadership election by 60% of the voting party members. He immediately became the chairman of the parliamentary party, succeeding Jeltje van Nieuwenhoven, and leaving her, Klaas de Vries and Jouke de Vries behind him by a 30% margin.
In the January 2003 election, Bos entered a head to head race with incumbent Prime Minister and leader of the Christian Democratic CDA, Jan Peter Balkenende. Under Bos the vote and seats of the PvdA nearly doubled from 15% (23 seats) in 2002 to 27% (42 seats) in 2003. This resurgence was partially credited to Bos' charisma and youthful appearance (and according to some journalists Bos' "sexy touch"). Balkenende's CDA however remained largest the party by a margin of two seats. The ensuing coalition formation talks between Balkenende and Bos failed after several months. The CDA went on to form a government with the conservative liberal VVD, and the progressive liberal D66.
At that time Bos was the leader of the largest opposition party. He spent considerable time reforming the PvdA's internal organisation and public image, together with the party's chairman Ruud Koole. He was criticized for his silence on important reforms and issues, and his moderacy which resulted in other parties claiming opposition leadership, among them most notably the Socialist Party. Although still enjoying large public support, criticism about his "style over substance" approach to politics was voiced in this period. At the December 2005 party congress, Bos announced that he aspired to become Prime Minister of the Netherlands, should the PvdA succeed in becoming the biggest party after the next parliament elections. And in the 2006 municipal elections, a few months lather, the PvdA performed particularly well, becoming the largest party in local government.
However, in the election campaign for the Dutch general elections of 2006 the PvdA – for the second time campaigning under his leadership – didn't manage to maintain this position as biggest party. Some considered pension reforms proposed by him to embattle the consequences of an aging population as a reason for this decline in popularity. Others emphasized a declining confidence in Bos among parts of the electorate that perceived him as "unreliable", as reason for this. Bos lost eight seats in the elections, which saw large gains for the main rival of Labour on the left side of the political spectrum, the more radical Socialist Party. Nonetheless, after these elections (and this time successful coalition talks with Prime Minister Balkenende), Bos became Deputy Prime Minister and Minister of Finance in the Fourth Balkenende cabinet, thereby breaking a campaign promise to only join a cabinet when he could hold the office of Prime Minister.
As part of the leadership of the PvdA he revoked his confidence in fellow party member Ella Vogelaar as Minister of Integration and Housing. She subsequently resigned her post on November 13, 2008. The Dutch parliamentary press chose him as politician of the year 2008, largely due to his crisis management of 2008/2009 world financial crisis that included nationalization of the Fortis bank.
In December 2002 Bos married Barbara Bos (the surname is a coincidence). The master of ceremonies of his marriage was Joop Wijn, the former State Secretary of finance for the CDA. Wouter and Barbara Bos have two daughters, Iris Jessie (5 February 2004) and Julia Roos (3 January 2006) and a son Joppe (18 April 2009)