Merabishvili was born in the largely Georgian Roman Catholic village of Ude in what is now Samtskhe-Javakheti region in south Georgia, then a Soviet republic. He graduated from the Georgian Technical University in 1992 with a degree from the Faculty of Mining. After his schooling he held several positions at the Technical University and at the Institute of Agriculture of Georgia before becoming a president of the Association for Protection of Landowners' Rights in 1995 and a co-founder of the Liberty Institute in 1996.
Merabishvili's direct involvement with politics began in November 1999 when he was elected to the Parliament of Georgia on the party ticket of the Union of Citizens of Georgia (UCG), chaired by then-President Eduard Shevardnadze. Merabishvili was a member of an influential and vocal, yet small, group of the UCG faction, known as “reformers” led by Zurab Zhvania and Mikheil Saakashvili and which called for more radical and Western-oriented political reforms.
In April 2001, with a simmering conflict in the UCG, Merabishvili, then a chairman of the Parliamentary Committee for Economic Policy, became the first and, at that time, the only leading member of the party to openly criticise Shevardnadze. In an interview with the Washington Post, Merabisvhili stated Shevardnadze was “tired” and lacked the political will to fight corruption. Shevardnadze downplayed the criticism, attributing Merabishvili’s statement to the latter's youth and inexperience.
In 2002, Merabishvili became Secretary General of Mikheil Saakashvili’s newly formed opposition National Movement. He was energetically involved in the protest movement following the November 2003 parliamentary elections which led to Shevardnadze’s resignation in the bloodless Rose Revolution.
After Saakashvili's ascent to the presidency, Merabishvili served as the National Security Advisor and Secretary of the National Security Council from January until June 2004 when he was appointed as Minister of State Security. In December 2004, the Ministry of State Security was merged with the Ministry of Internal Affairs of which Merabishvili was placed in charge. As interior minister, Merabishvili presided over police reform and a crackdown on criminal bosses, the so-called "thieves in law", winning praise from many international institutions and observers. Critics have accused the Interior Ministry of using excessive force and heavy-handed tactics in several cases, including against opposition protesters in 2007 and 2010. Merabishvili has denied these allegations.
In 2006, a controversy surrounding the murder of Sandro Girgvliani, a 28-year-old commercial bank employee, had a significant political fallout and was at the forefront of several opposition attempts to force Merabishvili to resign. Girgvliani's family accused interior ministry officials of murdering Sandro after he insulted them and Tako Salaqaia, Merabishvili's wife, during an argument in a café. The court case resulted in the conviction of four lower-level ministry officials, but the case was heavily criticized by several independent observers and opposition parties who claimed a cover up. Merabishvili himself accused the opposition parties of trying to use the Girgvliani murder case "for their political interests" and declared that he did not plan to resign.
By late 2008, Merabishvili had become one of the most influential figures in the government of Georgia. The Interior Ministry enlarged its responsibilities, taking greater control of border police and was designated by President Saakashvili to oversee distribution of the substantial international assistance for Georgians displaced in the August conflict with Russia. In a March 2009 interview with Rustavi 2 TV, Merabishvili said the assumption that he was the most powerful figure in Saakashvili's administration was "over-exaggerated", yet confirmed that in some cases the President had given him broader tasks.
In December 2011, Merabishvili's achievements as a Minister of Internal Affairs were praised by Bidzina Ivanishvili, a multi-billionaire businessman, who came into Georgian politics with the intent to challenge the government in the October 2012 parliamentary election. Ivanishvili called on Merabishvili to convince President Saakashvili to step down. Merabishvili later said he did not consider Ivanishvili to have been the government's "serious rival".
On June 30, 2012, President Saakashvili named Merabishvili as the country's Prime Minister, replacing Nika Gilauri. This decision was made a few months before the October parliamentary elections. Merabishvili said his program would be focused on the three key priorities: employment, agriculture development and availability of healthcare. He was approved by the Parliament of Georgia on July 4, 2012. The United National Movement lost majority of seats to the opposition coalition Bidzina Ivanishvili–Georgian Dream in the 2012 election. As envisaged by the constitution, Merabishvili and his government resigned on October 11, 2012, continuing to be an acting prime minister until Bidzina Ivanishvili was approved by the parliament on October 25, 2012. On October 15, 2012, Merabishvili was elected as secretary-general of the United National Movement, pledging to into "modern, new type of party".
On May 21, 2013, Merabishvili and Zurab Tchiaberashvili, governor of Kakheti, were arrested in connection to investigation into alleged misspending of GEL 5.2 million public funds on their party activists during the 2012 election campaign, leading to accusations of political vendetta leveled by the United National Movement against the Ivanishvili government.
On February 17, 2014 Merabishvili was sentenced to five years in jail after being found guilty of abuse of office, bribery of voters and inefficient use of budget funds. The Merabishvili defense team appealed the sentence. The opposition said it was a witch hunt of the former government. On 14 June 2016, the European Court of Human Rights ruled in Merabishvili v Georgia that the repeated extension of Merabishvili's pre-trial detention "lacked reasonableness" and was exploited "as an additional opportunity to obtain leverage over the unrelated investigation" into the death of the former Prime Minister Zurab Zhvania and financial activities of former President Mikheil Saakashvili.
Merabishvili is married to Tamar "Tako" Merabishvili née Salaqaia (born 1981). They have two sons, Misha (born 2000) and Davit (born 2009).