In February 1858 Bishop Mathias Loras died.  At that time, Bishop Clement Smyth, due to his status as Coadjutor Bishop, became the second Bishop of Dubuque.

Bishop Smyth carried on the work of building the Cathedral.  On July 7, 1861 the Cathedral received its formal dedication and blessing.  Despite the bitter Civil War that was being fought throughout the country, the Diocese experienced growth during Smyth’s years in office.  Smyth led the Diocese until his death on September 23, 1865.

Smyth was succeeded by John Hennessey, who was named to the Episcopate on April 24, 1866.  Bishop Hennessey was formally ordained and installed as Bishop on September 30, 1866.  Thus began a reign that would last well over a quarter of a century.

A number of changes were made to the Cathedral during Hennessey’s tenure as Bishop.  In 1876 the Cathedral’s tower was finally finished.  Originally intended to be made of stone, it was instead constructed of galvanized tin and wood after it was found that the pilings would not be able to support the weight.  The window in the tower is notable because it is the one thing that was built exactly as originally planned by Mullany.

Further changes were in store for the Cathedral building.  In 1882, Fridolin Heer – who directed the building of Sacred Heart Church and the Dubuque County Courthouse – directed the construction of the Blessed Sacrament Chapel.  Today we know this addition as the Cathedral Center.  The three stained glass windows that were originally in the sanctuary were moved to the Chapel – where they reside today.

In 1886, under the direction of architect J.J. Egan, a major renovation was done to the Cathedral.  The stained glass windows were lowered two feet.  The simpler vaulting designed by Mullany was taken down.  New capitals were built four feet lower on the clustered columns.  Iron arches were put up over the nave, and possibly over the outside aisles as well.  New groined vaulting, which was more steeply pitched, was built over the iron arches.  And finally the west wall of the tower was opened up to the interior of the Cathedral, complete with an arch conforming to the shape of the large lancet window on the east front of the tower.

Bishop Hennessey employed the services of Luigi Gregori to paint large frescos in the church.  Gregori painted the five large panels on the back of the sanctuary wall, as well as images of the saints in the gables of the arches in the nave of the Cathedral.  These works are still present in the Cathedral today.

In 1893 the Diocese of Dubuque was honored when it was raised to the level of an Archdiocese.  John Hennessey became the first Archbishop of Dubuque.

On March 4, 1900 Archbishop John Hennessey passed away.  His health had been declining, and he had recently suffered a stroke.  A large number of priests and members of the community packed the Cathedral for his funeral.

At the request of Archbishop Hennessey, the mortuary chapel was built in the basement of the Cathedral. Within this Chapel are the remains of Bishops Loras and Smyth, as well as Archbishops Hennessey, Francis Beckman, Henry Rohlman, Raymond Ettledorf, and James Byrne.