In 1833 the first permanent European settlement was established.  In July of 1833 Father Charles Felix Van Quickenborne celebrated mass in the river front home of Mrs. Brophy.  Father Van Quickenborne began planning for a parish building, but he was reassigned before any serious work could be done.  Father Van Quickenborne was followed by Father J. Fitzmaurice.  Fr. Fitzmaurice was pastor for only one year when he died in a cholera outbreak.

The next pastor was the renowned and revered Venerable Father Samuel Mazzuchelli, a Dominican priest, who came in 1835.  Father Samuel reorganized the parish, and named it St. Raphael’s after one of the three Archangels.

He designed and built this first Church building, which was completed in 1836.  This church was located just to the south of the current building where the school building stands today.

On July 28, 1837 the Diocese of Dubuque was created.  Fr. Mathias Loras was named the first Bishop of Dubuque.  He immediately went to Europe to recruit priests for the new diocese.  Bishop Mathias Loras arrived for the first time in Dubuque in 1839.  He found a growing community complete with a Catholic parish.  At this point St. Raphael’s was then raised to the status of a Cathedral.

In 1839, Fr. Mazzuchelli directed the construction of a large building at the back of the Cathedral.  This structure served the Bishop, and was the first home of St. Raphael’s Seminary – which today is known as Loras College.  Bishop Loras, Fr. Mazzuchelli, and other pioneer religious helped establish the presence of the church in what would become the state of Iowa.

In 1843 the Sisters of Charity of the Blessed Virgin Mary (B.V.M.) came to Dubuque from Philadelphia and began the first Cathedral School.

Following its founding in 1833, the city of Dubuque experienced rapid growth.  Soon the Cathedral was filled to capacity on Sundays.  A new church was planned on Main Street between 7th and 8th Streets to provide a second parish for the city.  A cornerstone was laid in 1849, but work never proceeded past the foundation.  Because of the crowding at the Cathedral, Loras created St. Patrick’s parish, and also created Holy Trinity (now Saint Mary’s) parish to minister to the increasing number of Germans in the city.

Loras realized that founding new parishes was only a temporary solution.  In 1857, in response to the rapid growth of Dubuque, Bishop Loras made plans to build a much larger Cathedral Church.  John Mullany was chosen to draw the plans for the new building – which would be over three times larger than the previous building.  Mullany used Magdalen College in Oxford, England as the model for the Cathedral.  Work began on land just to the north of the first Cathedral building.  The cornerstone was laid on Sunday, July 5, 1857, and was witnessed by a huge gathering.

During this time, the health of Bishop Loras began to fail.  Father Clement Smyth – a Trappist Father from the nearby New Melleray Abbey became the coadjutor to the Bishop of Dubuque and oversaw the building of the new Cathedral.  The structure was completed enough for Bishop Loras to offer the first mass in the new building on Christmas Day, 1857.  Less than two months later Bishop Pierre Jean Mathias Loras died.