[2] It is the mother church of the Diocese of Altoona-Johnstown and is the seat of its bishop, the Most Reverend Mark Leonard Bartchak.

The first Mass in Altoona was celebrated by the Reverend John Walsh, pastor of St. Mary Church in Hollidaysburg, Pennsylvania.

The first resident pastor was the Reverend John Tuigg, who was assigned by Bishop Michael O'Connor of the Diocese of Pittsburgh in 1853.

St. John's Pro-Cathedral was torn down to make room for the new building, and a temporary hall was built on Twelfth Avenue to serve as a place of worship.

The interior remained incomplete with walls of bare brick and rough concrete surrounding worshipers.

[8] Forty-eight stone steps rise in sections along a broad terrace from the street to the main entrance.

A Latin phrase is etched onto the stone wall along the staircase: Ecce tabernaculum Dei cum hominibus (Behold the dwelling place of God with men).

[6] The steel and reinforced concrete construction is covered with a veneer of Indiana limestone laid in courses of smooth-faced ashlar.

[5] The main doors into the cathedral are etched glass produced by Baut Studios of Pittsburgh, and they were installed when Monsignor Thomas Madden was pastor/rector (1972–1987).

They are flanked with doors that are etched with the traditional symbols of the four Evangelists: Matthew (angel), Luke (ox), Mark (lion), and John (eagle).

The baptismal font is placed at the entrance of the cathedral, serving to bring parishioners into the Church metaphorically.

Along the base of the dome and the sanctuary are also several symbols of the Eucharist: wheat, grapes, wine, loaves of bread, a fish, a monstrance, a chalice and host, and a pelican.

There are seven sanctuary stained glass windows that consist of The Annunciation, The Nativity, The Last Supper, The Crucifixion, The Resurrection, The Ascension, and The Crowning of Mary.

Six bishops and two rectors of the cathedral are entombed in the crypt chapel, with coat of arms erected on the crypt door: Eugene A. Garvey, John J. McCort, Richard T. Guilfoyle, Howard J. Carroll, J. Carroll McCormick and James J. Hogan.

The cathedral is home to an organ, built in 1931 by the German firm of G.F. Steinmeyer and Company, bearing the Opus Number 1543.

The organ stands below the stained glass window of Saint Cecilia, patroness of music and musicians.