While a student Molterer first engaged in politics; he became head of the Österreichische Studentenunion local branch at his university, and a member of the local students' council. By 1978, when a long-simmering policy conflict within the Austrian ÖSU developed towards a split in the party, Molterer supported liberal positions which sometimes were quite grossly at odds with the more conservative mainstream opinion of the ÖSU's main sponsor, the Austrian People's Party. Several Austrian journalists, consulters, entrepreneurs, academicians and finance people who enjoy national and international reputation today were Molterer's immediate peers in the ÖSU national executive board at this time. In 1980, he obtained his master's degree. From 1981 to 1984, Molterer was active in the Austrian Farmers' Association. Starting in 1987, he worked in the Ministry of Agriculture, under the ministers Josef Riegler and Franz Fischler.
Molterer served as Minister of Agriculture in the government of ChancellorFranz Vranitzky from 1994 until 2003. In 2003, Molterer became the chairman of the party's parliamentary club. Just like any other leading politician in Austria at any time, he found it hard to resist the opportunity to politically intervene in the workings of the state-owned national television agency, the ORF. In Molterer's case his critics coined the term Moltofon as a catchphrase for the particularly frequent phone callsthe agency reportedly received from his party office. On 9 January 2007, Molterer was chosen to become managing chairman of the party. He was formally elected chairman of the party at the federal party convention on 21 April 2007. By terminating his party's participation in the Grand Coalition with the SPÖ, he precipitated the early re-elections held on 28 September 2008, which ended in the worst result for the ÖVP since their respective inception after World War II. Wilhelm Molterer stepped down as chairman of the party on 29 September 2008 and was succeeded by Josef Pröll.
During his time in office, Molterer unsuccessfully opposed a 2007 deal between the Austrian government and the Eurofighter consortium on reducing an order of Eurofighter Typhoon military jets from 18 to 15 and to shift to a slightly less advanced model.
In 2013, Vienna prosecutors extended a corruption investigation to include Molterer and Foreign Ministry State Secretary Reinhold Lopatka on suspicion their ÖVP may have used Telekom Austria funds for illegal party financing in the 2008 election.