While the interior of the building was incomplete and temporary windows filled the spaces, the first Mass in the church was celebrated on Trinity Sunday in 1883.

The bells are named after the following saints: St. Anna, St. Bernard, St. Catherine, St. Cecilia, St. Edward, St. Elizabeth, St. Helen, St. John, St. Mary and St. Thomas.

From 1903 to 1945 the Cathedral operated St. Christopher's Inn, on Main Street, a Single Room Occupancy facility for homeless men.

It was replaced by a new dome, cupola and cross covered in 23-carat gold leaf in an effort led by Bishop John Cody in 1960.

A diocesan capital campaign, Gift of Faith, began in 2001 to provide necessary funds for another major renovation and restoration of the cathedral.