In the 2011 parliamentary election, she was re-elected to parliament. Although the ruling Liberal Party became the largest party and gained a seat and the Social Democrats lost a seat, the opposition parties combined obtained more seats than the government coalition. Her four-party bloc gained a majority of 89 seats in the 179-seat parliament against 86 for the sitting Prime Minister and his center-right parliamentary supporters. Prime Minister Lars Løkke Rasmussen formally tendered his resignation to Queen Margrethe on 16 September 2011. Rasmussen's cabinet remained in office as a caretaker government until 3 October, when Helle Thorning-Schmidt was appointed Prime Minister by the Queen following negotiations with the other opposition parties.
Helle Thorning-Schmidt officially began her first term as Prime Minister on 3 October 2011, after having presented her cabinet to the Queen and having received her official appointment. Thorning-Schmidt has pursued a centrist compromise agenda, building several reforms with support from both sides of the Folketing. This has caused friction with the supporting Red-Green Alliance, which has been kept outside of influence.
During the first year in office her government rolled back anti-immigration legislation enacted by the previous government, and passed a tax-reform with support from the liberal-conservative opposition. The tax reform raised the top tax threshold, effectively lowering tax rates for high income earners. The aim of the tax reform has been to increase labour output to fend off a projected shortage within the next decades. The stated goal is to entice Danes to work more in order to compensate for the decreasing workforce, by lowering tax on wages and gradually lowering welfare payments to those outside of the labour market to increase the economic benefit of working relative to receiving welfare. Despite effectively lowering tax rates on high income earners, tax revenue continued to increase from 831,172 million Krone in 2011, to 901,001 million Krone in 2013, and eventually reached 954,473 million Krone in 2015 by the end of her time in office. These effective reductions were in line with the 2009 tax reforms of Anders Fogh Rasmussen, a Venstre prime minister preceding her, which is likely why she received liberal-conservative support.
In November 2011, the daily Politiken disclosed that the Tax Ministry deputy chief Peter Loft had attended several meetings attending to the Thorning-Schmidt case and had tried to insert comments into the final resolution text. This would be unlawful under Danish law as the Tax Ministry may not interfere with the decisions taken in individual tax cases. This set off a flurry of speculation in the press, as to whether there had been any political pressure from the then government to pursue a stricter course in the tax case. The Tax Minister in the new government, Thor Möger Pedersen, subsequently asked Peter Loft and the director of the revenue service's Copenhagen branch, Erling Andersen, to give a report on the happenings. On 2 December, Pedersen disclosed that he had found such big discrepancies in the two reports that he would set up a commission of inquiry to determine the actual course of events.