Pierre Khảm was ordained to the priesthood on August 30, 1980, for the Archdiocese of Ho Chi Minh City, and then served as parochial vicar at Ha Dong church (1980–1983).

He served the parish until 1987 when he was transferred to Notre-Dame Cathedral Basilica of Saigon as parochial vicar and held this position until 1999.

On October 15, 2008, Pope Benedict XVI appointed him the Auxiliary Bishop of Archdiocese of Ho Chi Minh City.

On July 26, 2014, he was appointed as Bishop of Roman Catholic Diocese of Mỹ Tho by Pope Francis,[2] and was installed on August 30, 2014.

On July 13, 2016, Pope Francis appointed bishop Pierre Nguyễn Văn Khảm as a member of the Dicastery for Communication.