He was first President of the European Central Bank from 1998 until 2003, and was instrumental in the Introduction of the euro in the European Union in 2002. He was also credited for making numeral improvements for the Economy of the Netherlands.

Owing to the success of his monetary policy, he became well-known in other European countries, and this led to his appointment in 1998 as the first president of the new European Central Bank in Frankfurt, much to the chagrin of France, who wanted a French candidate. A compromise was agreed upon (although publicly denied by all parties) whereby Duisenberg would serve for at least four years, upon which the Frenchman Jean-Claude Trichet, director of the Banque de France, would take over. In 1999, Duisenberg received the Vision for Europe Award in recognition of his efforts toward the unification of Europe.

Duisenberg announced he would retire on 9 July 2003, (his 68th birthday), but he remained in office until Trichet was cleared of charges of fraud in connection with the collapse of the French bank Crédit Lyonnais. Trichet took over presidency of the ECB on 1 November 2003.

Duisenberg died in 2005 at the age of 70 while vacationing at his villa in Faucon near Orange, France. He drowned in his swimming pool after suffering a heart attack, a condition which may well also have been caused by his chain smoking.