During his studies at George Washington University, Pierluisi interned at the congressional office of then-Resident Commissioner of Puerto Rico Baltasar Corrada del Río.

[3] He was one of the principal attorneys representing the Government of Peru in its lawsuit against the Hunt Brothers, Nelson Bunker, William Herbert, and Lamar for attempting to corner the silver market in the late 1970s [4] He then practiced law in Puerto Rico from 1990 until 1993.

[7] In 1994, Pierluisi collaborated with President Bill Clinton's administration, contributing to the efforts that led to the enactment of the Violent Crime Control and Law Enforcement Act.

On May 18, 2007, Pedro Pierluisi declared his candidacy for the position of Resident Commissioner of Puerto Rico, a role that serves as the island's sole representative in the U.S. Congress.

However, he was defeated in the primary elections held on June 5, 2016, by Ricky Rosselló, who subsequently became the president of the New Progressive Party and went on to win the governorship.

[12] On May 18, 2007, Pierluisi announced his candidacy for Resident Commissioner, Puerto Rico's sole delegate to the United States Congress in the November 2008 elections.

The bill was passed by the House of Representatives but did not receive a vote in the Senate, and lapsed following the sine die adjournment of the 111th Congress.

On January 2, 2021, Pierluisi was inaugurated as Governor of Puerto Rico in a ceremony that, despite being well-attended, was held with a lower number of participants compared to previous events due to the COVID-19 pandemic.

[25][26] Pedro Pierluisi, similar to previous governors from the New Progressive Party (Spanish: Partido Nuevo Progresista, PNP) advocated for Puerto Rico's statehood during his campaign.

Following the 2020 general election, in which a plebiscite was held regarding the island's political status, Pierluisi vetoed a bill from the House that aimed to repeal HB-65-2020 and HB-167-2020.

On January 24, 2021, in response to the increasing incidents of gender-based violence, the Governor of Puerto Rico declared a state of emergency regarding this issue.

This action came in the aftermath of the tragic murder of Andrea Ruiz by her ex-partner, an event that the Governor cited as a clear failure of the system to protect victims of domestic violence.

Consequently, he directed the Secretary of Justice to ensure, whether through legislative or regulatory means, that a public prosecutor is always present in cases of domestic violence, aiming to strengthen the legal response to such incidents.

[28] On March 15, the Governor announced that the State of Emergency regarding maritime transportation to the islands of Vieques and Culebra would need to continue until 2022, coinciding with the conclusion of the privatization process for the ferry service.

[30] During the tenure of the Governor, a notable conflict arose between the executive branch and the legislature over the nomination of Elba Aponte for the position of Secretary of Education.

He asserted that the contract with LUMA Energy would not lead to higher electricity costs for consumers and argued that privatizing the power grid represents the best interest for the island's future.

This announcement was made in the presence of prominent leaders from the New Progressive Party (NPP), including former Senate President Thomas Rivera Schatz and San Juan Mayor Miguel Romero.

[35] In June 2024, Pedro Pierluisi obtained a hearing in the Senate of the United States of America, concerning draft statute 3231, from Democrat Martin Heinrich.

This measure is the Senate version of House Bill 2757 and provides for a binding plebiscite authorized by the U.S. Congress that allows residents of Puerto Rico to choose between U.S. statehood and full independence.

[citation needed] In an interview on August 28, he reaffirmed the press that he would be in fact running again, stating that "Puerto Rico is moving forward and there is no one who can stop us" and that they were "going to beat the PDP".

His brother, José Jaime Pierluisi, an economic adviser to then governor Pedro Rossello, was shot and killed during a carjacking in 1994.