The first Catholic presence in the present-day diocese was that of French missionaries in the 1640s attempting to evangelize the Mohawk peoples of the Haudenosaunee (Iroquois Confederation).

She spent the rest of her life working with native converts at a mission on the St. Lawrence River in New France.

Richard Coote, the first colonial governor, passed a law at the end of the 17th century that mandated a life sentence to any Catholic priest.

In 1784, the Vatican erected the Prefecture Apostolic of United States of America, covering the entire new nation.

Catholic immigrants began settling in the Capital District and the Mohawk Valley, establishing churches in these areas.

[11] Conroy increased the number of priests in the diocese, securing the services of the Augustinians and the Conventual Franciscans.

[13] In 1871, Pius IX selected Francis McNeirny of New York to serve as coadjutor bishop in Albany to assist Conroy.

[14] McNeirny recruited the Dominican Tertiaries, the Sisters of the Good Shepherd, and the Redemptorist Fathers to come to the diocese.

That same year, Thomas Martin Aloysius Burke was appointed the fourth bishop of Albany by Pope Leo XIII.

[17] During his administration, Burke enlarged the Boys' Asylum in Albany, reduced the diocesan debt, and renovated the cathedral.

[22] In 1945, William Scully of New York was appointed coadjutor bishop of Albany by Pope Pius XII to assist Gibbons.

The Religious Sisters of Mercy founded Maria College in Albany in 1958 to prepare women to join their order.

[28] During the event, Hubbard "expressed contrition and remorse for the centuries of anti-Jewish hostility promulgated under the Church's auspices".

[6][28] After Hubbard retired in 2014, Pope Francis named Edward Bernard Scharfenberger of the Diocese of Brooklyn as the next bishop of Albany.

[30] In 2018, Scharfenberger celebrated the feast day of Our Lady of Walsingham with Dean Leander Harding at the Episcopal Cathedral of All Saints in Albany.

[32][33] In September 2019, the AARP Foundation sued the diocese on behalf of a group of retired former employees of St. Clare's Hospital in Schenectady, which had closed in 2008.

A state investigation discovered that over several decades, the diocese had told employees that it was fully funding the St. Clare pension plan.

At his first retreat for diocesan clergy, Bishop McCloskey raised over $5,000 to start a building fund for a cathedral in the diocese.

Over 1,000 people attended the rededication mass, celebrated by Bishop Hubbard, Archbishop Timothy Dolan and Cardinal Edward Egan.

[42] In 2004, the Diocese of Albany reported that 19 priests had committed acts of sexual abuse over the previous 53 years.

[48][49] Hubbard later acknowledged that the diocese used to secretly send clergy accused of sexual abuse away for treatment rather than report them to police; he expressed regret for that practice.

[50] James Taylor of Saint Kateri Tekakwitha Parish in Niskayuna was arrested in April 2014 on charges of endangering the welfare of a minor.

He was accused of sending inappropriate photos to a 15-year-old girl in Round Lake, as well as texting her and making unforced physical contact.

[55] By March 2020, roughly 80 priests who had served in the diocese had been accused of committing acts of sex abuse.

[56] In May 2020, Cuomo signed a bill extending the lookback period contained in the Child Victims Act to January 2021.

[58] In March 2023, the Diocese of Albany would file for Chapter 11 bankruptcy in the face of numerous sexual abuse lawsuits.