Dzurinda was born on 4 February 1955 in the eastern Slovak village of Spišský Štvrtok. He graduated from the College of Transport and Communications in Žilina in 1979. In 1988, he completed his post-graduate scientific research there and was awarded with a Candidate of Sciences (CSc.) degree. He worked for the Transport Research Institute (VÚD) in Žilina as an economic analyst (1979–1988). Later he was the Director of an information Technology section within the regional directorate of the Czechoslovak Railways(ČSD) in Bratislava (1988–1990).

Dzurinda entered Slovak politics as one of the founding members of the Christian Democratic Movement (KDH), a conservative political party officially constituted in 1990. The first democratic general election in Czechoslovakia was held in 1990, and he was appointed Deputy Minister of Transportation and Posts of the Slovak Government in 1991. In 1992 he became a member of the Slovak parliament (National Council of the Slovak Republic, and worked as a member of the Committee for Budget and Finance. At the time of the split of Czechoslovakia and the establishment of an independent Slovakia (1993), he was KDH Deputy Chairman responsible for economy. During the tenure of Jozef Moravčík as Prime Minister (March–October 1994), Dzurinda was Minister of Transportation, Posts and Public Works. Following the 1994 general election, won by Vladimír Mečiar, he returned to the opposition benches in the parliament.

Dzurinda was appointed as Prime Minister for the first time in October 1998, leading five opposition parties united as the Slovak Democratic Coalition (SDK) and defeating the government of Vladimír Mečiar at the polls.

In January 2000 he founded a new political party, the Slovak Democratic and Christian Union (SDKÚ), which he has chaired since. In an intra-party election in March 2002, SDKU members confirmed his leading position and following the September 2002 general election he was given the opportunity to again form the Slovak government. The Party of the Hungarian Coalition (SMK), Christian Democratic Union (KDH) and the Alliance of the New Citizen (ANO) have joined the SDKU in the ruling coalition. The Free Forum split from the SDKU in early 2004.

Internationally, Dzurinda is perceived as a successful and progressive Politician, mostly due to the internationally acclaimed economic reforms his government implemented during Dzurinda's second government (2002-2006). In 2006 President of the United States George W. Bush called Dzurinda a friend and issued his admiration.

Dzurinda is a keen marathoner. He has taken part in the International Peace Marathon (MMM) in Košice 13 times, he ran the Lesser Carpathians Marathon (in 1986 in his personal best of 2 hours, 54 minutes and 57 seconds) and in 1996 the Rajec Marathon. In 2001, as Slovakia's premier he took part in the famous New York City Marathon, completing the 42.195-km course in 3 hours, 42 minutes. On 13 April 2003 he ran his second foreign marathon, held in London. He mended his final time at 3 hours 36 minutes. When speaking to the BBC presenter, he aired his hopes for a Slovakia as part of the EU, which occurred in 2004.

Mikuláš Dzurinda has been a regular MP in the National Council of the Slovak Republic since his party's defeat in the 2006 parliamentary elections. In February 2008, Juraj Liška, SDKÚ-DS's deputy leader, openly asked Dzurinda to resign as the party leader due to the low party polls and the arguably undemocratic style of leadership. The members of the party praesidium denied Mr. Liška's accusations and since the praesidium assembly, Mr. Liška has been unwilling to speak out on the inner affairs of the party. This affair led to the open protests against Mr. Dzurinda from party members from Bratislava. Since their exclusion from the party by a regular party judge there are no longer any thrills in the party.

During this period the budget deficit has been reduced to less than 3 percent of GDP, and it opened the door for Slovakia to join the eurozone in 2009. Economic growth, higher than 6 per cent, has become the fastest in the region. Nevertheless, foreign Investors has discovered the country, notably car companies such as PSA Peugeot-Citroën and Kia.

He was again elected to be the chairman of the SDKÚ-DS party on 6 November 2010 for next four years. He was only one candidate, the incumbent prime minister Radičová (from the same party) declined the nomination for candidacy.

Dzurinda later served as Minister of Foreign Affairs in Prime Minister Iveta Radičová's coalition government from 2010 to 2012. On 3 December 2013, Dzurinda was elected as President of the Centre for European Studies, the think-tank of the European People's Party, succeeding Wilfried Martens.

Dzurinda has lectured at North American and European universities, and to both experts and public audiences. He is a strong advocate of trans-Atlantic ties. He has met and talked personally to leading foreign politicians, including U.S. Presidents Bill Clinton and George W. Bush, German Chancellor Gerhard Schröder, British Prime Minister Tony Blair, European Commission President Romano Prodi, NATO Secretary General Lord George Robertson, and several influential US senators and congressmen. Under his leadership, the Visegrad Group—a co-operative grouping of the Czech Republic, Hungary, Poland and Slovakia—was revived and gained new stimuli.