[5] Nearly half of the country has approved Lacalle Pou's presidency thus far, with a September 2023 rating of 47% of the total population, the highest in the South American continent.

[7] He led Uruguay's response to the COVID-19 pandemic and vaccination rollout, for which he won praise and high approval ratings for his successful handling of the virus.

[8] In April 2020, his administration presented a bill under the constitutional label of "Urgent Consideration Law", which after being enacted on July 8, 2020, introduced reforms and restructuring in various areas.

[10] During his presidency, events occurred such as a drought that caused some protests due to the reduction in water availability and access in the Montevideo metropolitan area for a few weeks in mid-2023.

[11] In addition, a series of controversies arose with certain figures within his administration, resulting in several resignations such as Alejandro Astesiano, former chief custodian who was dismissed from his position and subsequently arrested for forging Uruguayan identity cards and passports to Russian citizens.

He was re-elected in 2004 under the Herrerist faction of the National Party, a movement founded by his great-grandfather, Luis Alberto de Herrera.

Lacalle Pou was a candidate for Intendant of Canelones in the 2010 municipal election,[24] obtaining 22.82% of the votes and being defeated by Marcos Carámbula of the Broad Front.

In the 2019 presidential primaries, Lacalle Pou competed against Enrique Antía, Carlos Iafigliola, Jorge Larrañaga and the new candidate Juan Sartori.

Lacalle Pou won by 53% of the votes, enough to announce Beatriz Argimón the same night of 30 June as a vice president candidate.

After the constitutional oath before the General Assembly, he paraded down with Vice President Beatriz Argimón along Libertador Avenue in a 1937 Ford V8 convertible that belonged to his great-grandfather, Luis Alberto de Herrera.

The left-wing party Frente Amplio deplores initiatives that could lead to a "setback" for the country, which risks becoming a "tax haven" again, as it was in the past.

[32] Lacalle had announced during his electoral campaign the introduction of a package of government measures through an urgent consideration law, a prerogative of the Executive Power in Uruguay that allows it to send to the General Assembly a bill with a peremptory term of 90 days, expired which is approved in the affirmative form if the General Assembly is not issued to the contrary.

"[41] In January 2021, the Lacalle government refused to recognize the new National Assembly, and stated that the Maduro's "dictatorial regime" violates the "rule of law.

"[42] Lacalle's government ordered the withdrawal of Uruguay from the Union of South American Nations (UNASUR), arguing that it occurred because "it is an organization that became an ideological political alliance contrary to the country's objectives of linking.

"[43] In addition, it was reported that the country would return to the Inter-American Treaty of Reciprocal Assistance (TIAR)[44] and that the government would support Luis Almagro in a re-election to the post of president of the Organization of American States.

[45][46] Lacalle Pou's government condemned the Russian invasion of Ukraine in February 2022 and advocated for the application of the Minsk agreements as a "peaceful and lasting" solution to the conflict.

[53][54] On April 17, he informed that his administration decided to create a group, made up of experts that would define methods and studies to advise the government.

[56] At the beginning, its measures were praised, when the country was facing a relative control of the situation and a low number of cases per day.

[57] In April 2020, the Lacalle administration presented a bill "of urgent consideration" –power of the Executive Branch of the Government according to Article 168 of the Constitution.

[62][63] Lacalle Pou married Lorena Ponce de León in 2000, in a service conducted by Daniel Sturla in the Montevideo Metropolitan Cathedral.