This resulted in outcry from his fellow Jesuits and censure by the church authorities in Rome, who exiled him to Nice in the Kingdom of Piedmont-Sardinia for several years.

Following his return to the United States, Mulledy was appointed as the first president of the College of the Holy Cross in 1843 and oversaw its establishment, including the construction of its first building.

In his later years, he was prolific in delivering sermons at Holy Cross, and played a role in seeing the college through investigations by the Know Nothing Party.

He then was assigned as pastor of Holy Trinity Church in Georgetown, and briefly as the superior at Saint Joseph's College in Philadelphia.

[11] He left the school in February 1815 to travel with nine others to White Marsh Manor in Prince George's County, Maryland, where they entered the Society of Jesus.

[17] In 1820, he was sent to study philosophy in Rome; on the voyage, he was accompanied by Charles Constantine Pise,[18] James Ryder, and George Fenwick.

[19] There, he studied at the Pontificio Collegio Urbano de Propaganda Fide for two years, and spent a further two as a tutor to the crown prince of Naples.

[11] He left from the port of Livorno on a treacherous voyage that lasted 171 days, and caused some in the United States to fear that the three Jesuits aboard had perished.

[28] During his presidency, the Jesuit Ratio Studiorum was more fully implemented, primarily under the direction of the prefect of studies, George Fenwick.

[29] With a growth in the number of books owned by the university under Mulledy's presidency, he undertook to organize the 12,000 volumes in a single library room in Old North on February 16, 1831.

[32] In March 1833, Pope Gregory XVI chartered Georgetown College as an ecclesiastical university, the first such institution in the United States.

[35] Kenney reported back to Rome that Mulledy had been a successful administrator despite his "extremely impetuous enthusiasm and excessive patriotism.

He was initially unable to fund a new building that would house a refectory, chapel, study hall, and dormitories; eventually, a Jesuit who owned property because he had not yet taken final vows offered Mulledy a substantial loan.

[45] In 1848, due to popular uprisings in the Italian states, many Jesuits fled Italy and took refuge for a time at Georgetown College, including the future famed astronomer Angelo Secchi and scientist Giambattista Pianciani.

[49] In 1838, Bishop Benedict Joseph Fenwick appointed Mulledy vicar general of the Diocese of Boston, which he held simultaneously as provincial superior.

Compounding the financial insecurity was that the Maryland Jesuits' plantations had been mismanaged and were not generating sufficient income to support the college.

This plan had been authorized by the Jesuit Superior General in Rome, Jan Roothaan,[18] in late 1838 on the condition that the slave families not be separated and that they be sold to owners who would allow them to continue in their Catholic faith.

William McSherry convinced Roothaan to delay his decision and, along with Samuel Eccleston (the Archbishop of Baltimore), tried to persuade Mulledy to step down.

[18] By the time Roothaan came to this decision, McSherry had already convinced Mulledy to step down in late June and to go to Rome to explain himself to the church authorities.

Following Mulledy's meeting with Roothaan in Rome, he was assigned to teach English to young boys in Nice in the Kingdom of Piedmont-Sardinia,[56][57] effectively as censure for his conduct in the slave sale affair.

[65] In light of steadily increasing enrollment and accompanying overcrowding, the college was greatly aided by a donation of $1,000 (~$32,008 in 2023) from Andrew Carney in March 1844.

A Belgian Jesuit, Peter Verhaegen, wrote to Roothaan that Mulledy had been "imperious and despotic," and severely condemned his hostile temperament and breach of fraternity.

[67] The new provincial superior, Ignatius Brocard, transferred Mulledy to Philadelphia, where he continued as procurator,[60] before being sent to Frederick, Maryland in 1850 as president of St. John's Literary Institution, succeeding Charles H. Stonestreet.

[5] Mulledy advocated for an English-only curriculum, rather than teaching classes in Latin, so as to not drive away students into Protestant schools that taught in English.

[72] With the rise of the Know Nothing movement across the United States, and the 1854 victory of the party in winning control of the Massachusetts General Court, a Joint Special Committee on the Inspection of Nunneries and Convents was formed to investigate Catholic institutions.

A rumor began circulating in July of that year that Holy Cross was being used as a weapons depot for an eventual Catholic revolution.

The intent of this dual name was to retain its recognition of Mulledy as a founder of the college, while simultaneously recognizing John E. Brooks, who worked to racially integrate the campus of Holy Cross in 1968 and who later was its president.