Vestager has been a professional politician since the age of 21, when she was appointed to the central board and executive committee of the SLP and its European Affairs Committee, and shortly afterwards as National Chairwoman of the Party.
On 15 June 2007 Vestager secured election as her Party's parliamentary group leader in the Folketing, replacing Marianne Jelved. When Denmark’s Prime MinisterLars Løkke Rasmussen called an early election in 2011 after failing to secure majority lawmaker backing for his economic stimulus package, Vestager’s Social Liberals and the Conservative People’s Party formed a political alliance, pledging to work together no matter which political bloc would win the election.
From 2011 until 2014 Vestager served as Minister for Economic and Interior Affairs in the three-party Social Democrat-led coalition government of Helle Thorning-Schmidt. Having forced through deep cuts in unemployment benefits of Denmark's generous social welfare system after the country's economy narrowly escaped recession in 2012, she was at one point considered by Danish media and pollsters as the most powerful person in government, even above Thorning-Schmidt.
In her time in office, chaired the meetings of economic and finance ministers of the European Union (ECOFIN) during Denmark’s presidency of the Council of Ministers in 2012. In this capacity, she announced that the European Union would cede two of its seats on the board of the International Monetary Fund to emerging economies under a new power-sharing scheme for international financial institutions. She also worked closely with Jean-Claude Juncker to salvage Europe’s financial sector and forge a European Banking Union.
Between 2011 and 2014, Vestager led Denmark’s campaign against Basel III liquidity rules, arguing in favor of allowing banks to use 75 percent more in covered bonds to fill liquidity buffers than allowed under Basel III rules; at the time; Denmark’s $550 billion mortgage-backed covered bond market, part of the country’s two-century-old mortgage system, was the world’s largest per capita. Meanwhile, in 2013 she repeatedly ruled out slowing down steps toward stricter requirements for systemically important lenders and reiterated her stance that banks won’t get tax breaks to help them through the transition caused by regulatory reform.
In May 2014, Vestager presented a growth package designed to drag Denmark’s economy – at the time Scandinavia’s weakest – out of its crisis, raising the country’s structural output by 6 billion kroner ($1.1 billion) and cut costs for companies by 4 billion kroner in 2020 through 89 measures to improve the business climate and boost employment.
On 31 August 2014, Prime Minister Thorning-Schmidt nominated Vestager as Denmark's EU Commissioner in the Juncker Commission. Despite her repeated denials of campaigning for the Environment portfolio, eventually she was designated the Competition dossier in the Juncker Commission. On 3 October 2014, she won the European Parliament's backing following her confirmation hearing.
In her confirmation hearings, Vestager said she favored reaching settlement of cases before they come to her for a final executive judgment, usually for reduced fines or negotiated concessions from the companies.
Like her predecessor, Joaquín Almunia, Vestager has since been focusing on state aid cases. Within few months in the office, she brought antitrust charges against Google; Almunia had initially opened the investigation into Google in 2010, and had reached a settlement deal with Google by 2014 but was unable to convince the European Commission to accept it before his term ended. Vestager inherited Almunia's case but has shown greater desire to continue pursuing Google/Alphabet over the alleged antitrust violations. Also, she initiated investigations into the tax affairs of Fiat, Starbucks, Amazon.com and Apple Inc. under competition rules. In 2014, she launched proceedings against Gazprom, one of Europe's main gas suppliers, over allegations of breaching EU antitrust rules by putting in place artificial barriers to trade with eight European countries: Estonia, Latvia, Lithuania, Poland, Czech Republic, Slovakia, Hungary and Bulgaria.
In January 2015, Vestager ordered Cyprus Airways to pay back over 65 million euros in illegal state aid received in 2012 and 2013 as part of a restructuring package; as a consequence, Cyprus suspended operations at its flag carrier resulting in 550 job losses and reduced competition.