[1][4] In 1821, Spalding entered St. Mary's College in Lebanon, Kentucky,[3] where he became a favorite pupil of the school founder, Reverend William Byrne.

He received the degree after a marathon session defending 256 propositions on theology, church history, and canon law from attacks by university faculty and other scholars.

[1] While in Rome, Spalding was ordained a priest for the Diocese of Bardstown by Cardinal Carlo Maria Pedicini on August 13, 1834.

Bishop Francis Kenrick, his former professor at St. Thomas Seminary, allowed Spalding to preach his first homily at Saint John the Evangelist Cathedral in Philadelphia.

[4] After Spalding arrived in Bardstown in December 1834, Flaget named him rector of St. Joseph's Cathedral and professor of philosophy at St. Thomas Seminary.

He received his episcopal consecration on September 1, 1848, from Flaget, with Bishops Francis Kenrick and Richard Miles serving as co-consecrators, at St. Louis Cathedral in Louisville.

[6] At the time of Spalding's ascension, the diocese comprised the entire state of Kentucky and included over 30,000 Catholics, 43 churches, 10 chapels, and 40 priests.

[1][10] Spalding completed construction of Cathedral of the Assumption in Louisville in 1852, with Archbishop John Baptist Purcell dedicating it in October 1852.

In order to address the shortage of clergy in his diocese, Spalding traveled Europe for a year and recruited the services of a number of priests and the Xaverian Brothers.

Political opponents of the Democratic Party and supporters of the Know Nothing movement claimed that foreign-born Catholics intended to subvert the government, and Spalding himself was accused of harboring weapons in various churches.

[11] Following the riots' end, Spalding wrote, "I entreat all to pause and reflect, to commit no violence, to believe no idle rumors, and to cultivate that peace and love which are characteristics of the religion of Christ.

Although he sought to avoid "angry political discussions",[3] he published a piece on the war in L'Osservatore Romano that clearly demonstrated his sympathy laid with the Confederacy.

[6][13] After founding the House of the Good Shepherd, Spalding conducted a visitation of the archdiocese, during which he administered Confirmation to 8,000 people.

[2] Following the end of the civil war, Spalding appealed for financial aid to people in the former Confederacy, posing the question, "Can we be held blameless before God if our brethren, whom we are solemnly commanded to love even as ourselves, should perish through our coldness and neglect?

"[8] Spalding invited Revered Herbert Vaughan and the Mill Hill Fathers from England to minister exclusively among freedmen.

[2][15] In 1866, Spalding recruited four monks of the Xaverian Brothers from Belgium to found St. Mary's Industrial School, a facility for homeless boys.

However, the capture of Rome by King Victor Emmanuel II in 1870, during the war for the unification of Italy, forced the canceling of the council.

[3] However, he published a piece on the American Civil War in L'Osservatore Romano that showed his sympathy for the Confederate States of America.

"[12] While he firmly believed in papal infallibility, Spalding initially considered that its dogmatic definition would be unnecessary and inexpedient.

[1] Spalding stated: I should regard as the greatest misfortune of my life to have contributed in any way whatever to cause even a single one of my brothers to falter in perfect obedience to the authority of the Church.

[4]Immediately after the final vote on infallibility, he addressed a pastoral letter to Baltimore, in which he explained the necessity of such a definition and attacked what he felt were numerous misrepresentations.

[2] In 1865, Spalding issued a defense of Pius IX's Syllabus of Errors, which many Americans viewed as a condemnation of the basic principles of their system of government.

[1] For instance, Spalding declared: Freedom of worship is condemned when it implies a right not given by Christ, and insists on the right of introducing false religion into a country where it does not exist.