The Santer Commission was the European Commission in office between 23 January 1995 and 15 March 1999. The administration was led by Jacques Santer (former Prime Minister of Luxembourg).

The body had 20 members and oversaw the introduction of the euro. It was cut short when the Commission became the first to resign en masse, owing to allegations of corruption. Some members continued under Manuel Marín until the Prodi Commission was appointed.

In 1994, Jacques Delors was due to step down from a successful tenure as President of the European Commission. However, his federalist style was not to the liking of many national governments. Hence, when Jean-Luc Dehaene (the then Prime Minister of Belgium) was nominated as his successor, he was vetoed by the UK on the grounds he was too federalist. Jacques Santer, then-Prime Minister of Luxembourg, was seen as less federalist, for his presidency had earlier proposed the pillar structure. Hence, he was nominated and approved by the European Council on 15 July 1994.

Being seen as the "second choice" weakened Santer's position, with the European Parliament approving him only by a narrow majority. He himself admitted that he "was not the first choice – but to become Commission president was not my first choice either." He did, however, flex his powers over the nominations for the other Commissioners. The President gained this power under the Maastricht Treaty that came into force the previous year. On 18 January 1995, he got his Commission approved by Parliament by 416 votes to 103 (a larger majority than expected) and they were appointed by the council on 23 January.

The Santer Commission oversaw the development of the Treaty of Nice before it was signed in 2000, negotiations with those countries to join in 2004 and the signing of the Amsterdam Treaty in 1997.

Notably it contributed to the development of the euro and issued a series of green papers based on Commissioner Yves-Thibault de Silguy's work. The commission also developed the euro currency symbol. The euro was established on 1999-01-01. The commission also continued Delors's social agenda, pushed for more powers in that field including tackling unemployment and began proposals for the reform of the Common Agricultural Policy.

Santer, desiring a quotable slogan for his administration, stated his Commissions aim would be "to do less, but do it better" (a slogan adopted and adapted by many since). Although just a sound bite, it struck a chord for some thinking the Community needed a rest after the new treaties and the euro, even if the nature of the Community itself requires movements and new projects to keep it busy. However, during 1998 the commission began to lose authority due to management criticisms from the Parliament.

The community's budget for each year needs to be discharged by the Parliament following its report by the European Court of Auditors. It had only refused to do so once previously, in 1984. Towards the end of 1998 the Parliament's Committee on Budgetary Control initially refused to discharge the community's budget for 1996 over what it saw as the arrogance of the Commission in its refusal to answer questions relating to financial mismanagement. Paul van Buitenen, a whistle-blower working in the commission, had sent the Parliament a report alleging widespread fraud and cover ups, stating: "I found strong indications that . . . auditors have been hindered in their investigations and that officials received instructions to obstruct the audit examinations . . . The commission is a closed culture and they want to keep it that way, and my objective is to open it up, to create more transparency and to put power where it belongs – and that's in the democratically-elected European Parliament." In response, the Commission suspended him on half pay for releasing details of an inquiry.