1985–2004: Priesthood

He was ordained priest on October 5, 1985, and bishop on August 31, 2001, by Cardinal Jaime Sin whom he served as private secretary for fifteen years and as Vicar General for 13 years. He then became the first Rector of the EDSA Shrine and Vicar General of the Archdiocese of Manila in concurrent capacity.

Appointed auxiliary bishop of Manila on July 25, 2001, he was ordained to the episcopacy on August 31, 2001, until his transfer to Balanga on July 3, 2004. Before his election as president of the bishops' conference, he was Bishop Chairman of the Episcopal Commission for Catechesis and Catholic Education. He is the current Bishop Chairman of the Episcopal Commission for Seminaries since 2019 until 2026.

2004–2009: Bishop of Balanga

He became Bishop of Balanga from July 3, 2004, until his transfer to Lingayen-Dagupan on November 4, 2009.

During his tenure as Bishop of Balanga, he saw that the cathedral's decorations were in bad shape; he renovated the inside with a new design. When it was finished, the white walls were replaced by a wall of bricks, the structure behind the altar became marble white, the floors were higher, the lectern bearing the coat of arms of diocese of Balanga was replaced with the one with Holy Spirit, and the chandeliers were replaced by ceiling lights.

In 2008, 15 life-size images of saints with their names were added outside the cathedral representing the patron saints from the 11 towns and 1 city of Bataan where the Diocese of Balanga has jurisdiction with and a few towns have multiple saints.

On December 8, 2008, the Clinica Diocesano de San Jose was founded which is a weekly medical and dental mission for the poor people of Bataan.

Few months before he became archbishop of Lingayen-Dagupan in Pangasinan on November 2009, images featuring the ancestors of Jesus and image of Jesus Christ at the cathedral's dome were added.

On November 2, 2009, he held his final mass as Bishop of Balanga as a preparation for ending his tenure as the diocese's bishop and starting his term as archbishop of Lingayen-Dagupan in Pangasinan.^[5]

2009–present: Archbishop of Lingayen-Dagupan

Pope Benedict XVI named Villegas as archbishop of Lingayen-Dagupan on September 8, 2009, to succeed Oscar Cruz. He then became the archdiocese's archbishop upon his installation on November 4, 2009, ending his 5 years and 4 months tenure as Bishop of Balanga. Due to the sudden death of the Roman Catholic Bishop of San Fernando de La Union of San Fernando de La Union Bishop Artemio Rillera, he was also appointed Apostolic Administrator of the said vacant See from November 16, 2011, until October 11, 2012, in a concurrent capacity.

He was the Chairman of the Episcopal Commission for Catechesis and Catholic Education of the CBCP from 2003 until 2012 and formerly a member of the Presidential Committee of the Pontifical Council for the Family. He is currently the Chairman of the CBCP Episcopal Commission for Seminaries.

He joined the Order of Preachers.^[6] He is a chaplain of the Order of Malta and the Equestrian Order of the Holy Sepulchre.

He was a synodal father in the Synod of Bishops of 2012 and 2014. He is a member of the Council of the papal foundation Aid to the Church in Need.

As of February 2021, he has ordained 234 deacons and 210 priests since his episcopal ordination. In the Archdiocese of Lingayen Dagupan, he has decreed the creation of twelve new parishes and nine quasi parishes, since his installation as archbishop on November 4, 2009, by opening the archdiocese to the missionary presence of religious priests.

He opened the first diocesan theology seminary in northern Philippines in 2013 called Mary Help of Christians Theology Seminary which grants civil master's degrees in theology and pastoral ministry.

Political involvement

Villegas' views on social and political issues in the Philippines have not been without controversy, mainly regarding high-profile issues such as the Reproductive Health Bill, the re-imposition of death penalty (long-opposed by the Catholic Church),^[8] human rights violations, extrajudicial killings under the Duterte administration, and the burial of dictator Ferdinand Marcos at the Libingan ng mga Bayani (Heroes' Cemetery).^[9][10]

Following the 31st Anniversary of the 1986 EDSA People Power Revolution on February 25, 2017, Villegas published a 'letter' to his mentor, Cardinal Jaime Sin, where he denounced corruption, extrajudicial killings, and the restoration of the Marcos family to political power under the Duterte administration. Villegas lamented that "the dictator ousted by People Power is now buried among heroes. The Lady of one thousand two hundred pairs of shoes is now Representative in Congress."^[11] Villegas' remarks were criticized by Duterte's daughter, then-Davao City mayor and now Vice President Sara Duterte-Carpio, who described Villegas as "worse than a hundred President Dutertes".^[12]

On July 19, 2019, the PNP–Criminal Investigation and Detection Group (CIDG) filed charges against Villegas and members of the opposition for "sedition, cyber libel, libel, estafa, harboring a criminal, and obstruction of justice".^[13][14] Members of the opposition, as well as local and international human rights groups including Human Rights Watch and Amnesty International, denounced the charges as a politically motivated move intended to silence criticism of Duterte and his presidency.^[15][16][17] The charges were eventually dropped because of lack of evidence.^[18]

In regards to vote buying, Villegas expressed the position that a voters who accept money from people to vote for certain politicians may not be necessarily committing a sin – if the voter does not fulfill their agreement even if they accept the money.^[19]

Due to the non-renewal of broadcast franchise application of ABS-CBN, Villegas expressed that the network's issues could have been dealt in with proper proceedings.^[20] In October 2023, Villegas publicly stated that the International Criminal Court investigators should be allowed to probe into allegations of human rights abuses in Duterte's war on drugs.^[21]