The earliest Catholic mission in the Lehigh Valley was established in the 1720s in Goshenhoppen, whose residents came from a community in Philadelphia.

During the Feast of Corpus Christi, some Protestant residents of Goshenhoppen mistook a Catholic procession for a military drill and complained to the colonial governor.

Catholic missionaries and army chaplains tended to wounded and sick American and French soldiers at a military hospital in Allentown.

[2] After the discovery of anthracite coal in the region, Catholic immigrants started moving in to work in the mines and related industries.

McShea also founded "Operation Rice Bowl", which began in the form of a small cardboard box in the parishes of the diocese to receive alms directed to relieving a famine in Africa.

[11] He founded Holy Family Manor, a nursing and rehabilitation center at Eugene Grace's former mansion in Bethlehem.

[13] Welsh established the first Youth Ministry Office in the diocese and raised $13 million in an endowment campaign for diocesan schools and other educational efforts,[14] improved relations between Catholics and Jews and founded both AD Times, a diocesan newspaper, and Catholic Distance University.

In 2008, Pope Benedict XVI named Monsignor John Barres from the Diocese of Wilmington as the bishop of Allentown.

[19] During his tenure, Barres established the Saint Thomas More Society for lawyers, and expanded the diocese's Hispanic ministry and evangelization.

In 2016, Alfred Schlert was named by Pope Francis as bishop of the Diocese of Allentown, and has served continuously since.

[21] Reverend Thomas J. Bender in 1972 was discovered by a Pennsylvania State Trooper sitting in a parked car with a student from Nativity High School.

[22] In 1981, a parent reported to the archdiocese that his 12 year old son had been sexually molested that day by Reverend Michael S. Lawrence at St. Catharine of Siena Parish in Mount Penn.

[23] Reverend Ronald J. Yarrosh, assistant pastor of St. Ambrose Catholic Church in Schuylkill Haven, was arrested in May 2004 on charges of possessing child pornography.

[27] That same month, the grand jury report named 37 priests in the diocese with credible accusations of sexual misconduct over several decades.

[28] Bishop Schlert stated that the cases dated back decades and that most of the accused priests were dead or no longer active in the ministry.

The diocese removed three priests from ministry after the grand jury report was released; however, one was reinstated when the allegation was determined to be unfounded.

In August 2018, Reverend Kevin Lonergan was charged with indecent assault and corruption of minors after inappropriately touching a 17-year-old girl and sending nude images of himself to her.

In September 2018, the Berks County District Attorney's Office exonerated Gillis after the girl recanted her accusations.

[34] District Attorney John T. Adams said, "It is unfortunate that the accusation of child sexual abuse against Reverend Gillis was made public by the Diocese of Orlando before the outcome of this investigation could be determined.