As provincial superior, Stonestreet worked with Anthony Ciampi in the aftermath of the devastating fire at the College of the Holy Cross, and addressed growing anti-Catholicism.

Owing to violence from the Know Nothings, he forbade Jesuits from wearing their clerical attire in public or being addressed by their ecclesiastical titles.

In 1863, Stonestreet was involved in the legal incorporation of Boston College, and testified in court as to his knowledge of the conspirators in the assassination of President Abraham Lincoln, specifically Mary Surratt and Samuel Mudd.

Charles attended a classical school run by Philip Briscoe in St. Mary's County, before enrolling in Georgetown University in Washington, D.C., where he graduated in 1833.

[3] He was sent on a mission to Alexandria, Virginia,[3] before being appointed president of St. John's Literary Institution in Frederick, Maryland, in 1848,[17] where he remained until 1850.

[4] At the same time, he was assigned to St. John the Evangelist Church in Frederick, Maryland, as an assistant curate to Thomas Lilly.

[21] In May 1852, he commemorated the landing of the Catholic pilgrims in the Maryland Colony by traveling to St. Inigoes, Maryland, with Bishops James Oliver Van de Velde of Chicago, Richard Pius Miles of Nashville, and John Baptist Miège of the Indian Territory East of the Rocky Mountains.

[24] During this time, the Georgetown library saw significant growth, including almost 900 books that Stonestreet had shipped from Rome.

This period of growth was so substantial that the library in Old North became filled to capacity, and Stonestreet sought to construct a larger facility.

[26] That August, he accepted an appointment as provincial superior of the Maryland Province of the Society of Jesus; Bernard A. Maguire was named as his successor.

The new Superior General, Peter Beckx, proposed in 1855 that Georgetown be transformed into such a scholasticate for training all the Jesuits in the United States, and cease educating lay students.

[35] Stonestreet responded to increasing anti-Catholicism in Maryland, specifically the allegation that the Jesuits swore an oath to the pope to overthrow the United States, by writing a letter to local newspapers in February 1855 in which he described his patriotic pride and attachment to his childhood home on the Western Shore of Maryland.

"[37] Upon the selection of Burchard Villiger as the provincial superior of the Maryland province, Stonestreet succeeded him as president of the Washington Seminary on April 25, 1858.

[39] Very shortly thereafter, on May 4, 1858, President James Buchanan signed into law the bill independently chartering the Washington Seminary, and recognizing the institution by its new name of Gonzaga College.

[39] As president of Gonzaga, Stonestreet led the opening prayer of the House of Representatives on January 24, 1859, and of the Senate on February 9, 1859.

However, the majority of Jesuits and students at the school were aligned with the Confederacy; members of Stonestreet's family fought in the war for the South.

[53] He was also called to testify about Samuel Mudd, the physician who attended to John Wilkes Booth's fractured leg.

[56] When the president of Gonzaga College and rector of St. Aloysius Church, Bernardin F. Wiget, fell ill in 1868, Stonestreet was temporarily again appointed to the two offices, until August 1869 when James Clark became the permanent replacement.

The new provincial superior, Joseph Keller, decided against the nomination, due to his age; instead, John Early was appointed.