Born in Wilmington, Delaware, United States, to parents who had left Latvia during the Soviet occupation, he was active in the American Latvian community throughout his youth.

[2] After graduating with a bachelor's degree summa cum laude and PhD in linguistics from the University of Pennsylvania, Kariņš moved to Latvia in 1997 and founded a frozen food business.

[10] He announced his resignation as prime minister on 14 August 2023 due to conflicts within the coalition led by his party[11] and left office upon election of his successor on 15 September 2023.

[7] As child refugees, his parents, with their respective families, fled the Soviet re-occupation of Latvia in 1944, grew up, met and married in Sweden before migrating to the United States.

[16] From 1984 to 1986, he studied at St. John's College in Annapolis, Maryland, before switching to a linguistics program at the University of Pennsylvania where he graduated summa cum laude in 1988.

[33] On 7 January 2019, he was tasked by Latvian President Raimonds Vējonis with forming the next government, following the failures of previous nominees Jānis Bordāns and Aldis Gobzems in a contentious negotiation process.

[6] Mayor of Ventspils Aivars Lembergs called on Kariņš, a dual citizen of both the United States and Latvia, to give up his American citizenship while the prime minister,[34] but he refused to do so.

[37] On September 9, the Latvian Association of Journalists criticized Kariņš for not participating in public debates and being overly selective for which interview programs he appeared on.

[38] During his confirmation session, Kariņš promised that his government would be "evolutionary, not revolutionary”, and announced a seven-point program that prioritized financial sector reform, implementing anti-corruption measures, continuing the Kučinskis government's education reforms, improving but not overhauling the health care system, eliminating the controversial green energy subsidy, reducing the number of administrative divisions, and addressing "demographic issues.

"[39] On 5 April 2019, he supported Minister of Environmental Protection and Regional Development Juris Pūce's action in dismissing long-serving Mayor of Riga Nils Ušakovs from his position due to multiple violations of the law.

[40] On 13 June 2019, the Saeima approved measures that allowed Latvian institutions to implement UN sanctions more quickly, reduced the Financial and Capital Market Commission from five members to just three, and made these commissioners' positions subject to appointment by parliament.

[41] Commission chairman Peters Putniņš protested that the measures would allow politicians to have greater control of what should be a non-political regulatory body.

[2] On 30 March, Minister for Education Inga Šuplinska claimed that money to finance the planned wage increases could be found by mid-May.

[49] In April 2019, the Kariņš government announced a proposal for four tiers of minimum student numbers for schools based on the municipality's size and location.

[52] In June 2022, Saeima approved a government proposal to accelerate the transition to Latvian language-only instruction at preschool and primary levels of the education system so that it would be completed by the year 2025.

On 16 September 2022, a strike by education sector workers was narrowly avoided when a compromise agreement to raise teachers' salaries and balance their workloads between contact hours and preparation hours was reached between the Kariņš government and the Latvian Trade Union of Education and Science Employees just three days before the indefinite strike was set to begin.

[8] On that day, in a phone interview with Latvian Public Radio, he committed to canceling the subsidy within a reasonable timeframe and argued that the Minister of Economics, Ralfs Nemiro, Gobzems's former party member, had already published a report proving that doing so by the end of March was a legal impossibility.

[64] On his first official visit to Brussels on 22 February 2019, Kariņš assured that Latvia would maintain a "Euro-Atlantic course," and that Brexit negotiator Michel Barnier had his full support.

[65] He addressed European Parliament on 17 April, arguing that it was "useless" to fight against the rise of populism and that it was necessary to understand why people listened to the promises of populists.

On 23 August, Kariņš joined the prime ministers of Poland, Lithuania, and Estonia in releasing a statement that blamed Belarusian president Alexander Lukashenko for "using immigrants to destabilize neighbouring countries".

At the Riga StratCom Dialogue in May 2022, Kariņš said that, "in order to ensure peace and security in Europe and the world, Russia must lose this war.

On 23 February 2022, one day before Russia's invasion of Ukraine, Latvia delivered FIM-92 Stinger surface-to-air missiles to the Ukrainian Armed Forces.

[78] On 12 March 2020, Kariņš announced a state of emergency in response to the COVID-19 pandemic, declaring that schools would be closed as of the next day and begin distance learning in addition to large gatherings being banned.

[89] On October 20, the Kariņš government implemented a month-long "lockdown" in response to requests from the medical sector and Minister of Health Daniels Pavļuts.

[90] The same day, the government approved amendments that would allow employers to terminate contracts with employees who do not have a valid certificate of vaccination or recovery from COVID-19.

On 28 November, he announced his intention to seek the nomination to become the next Secretary General of NATO, saying that the alliance needed a consensus builder who is committed to higher defense spending and possessed a clear vision in managing relations with Russia.

[101] In March 2019, Saeima Deputy Aldis Gobzems asked law enforcement officials to investigate a Skolas iela 2 property transaction between Kariņš and wife Kariņa from one side and Russian citizens, who are associated with Gazprom International and Government of Moscow from another, that he alleged could be related to money laundering and tax avoidance.