Born in Annapolis, Maryland, on 22 November 1801, "the son of an Italian father and a mother who came from an old Philadelphia family,"[2] he was educated at Georgetown College in Washington, D.C., sent to Rome to continue studies, and entered the Society of Jesus as a novice.

At this point, he was also made a knight of the Holy Roman Empire[dubious – discuss] and was granted a Doctor of Divinity degree by examination.

[1] Answering objections to the presence of a Catholic in such a prominent government role, and prefiguring a similar speech by John F. Kennedy more than 125 years later, on July 4, 1833, Pise made "an eloquent address" before the Maryland House of Delegates describing in what sense he felt an American Roman Catholic owed 'allegiance' to the Pope.

Alternatively, the same biographer suggests that it may have been an anti-Irish, anti-Jesuit streak in Ambrose Maréchal, Bishop of Baltimore, which led him to suppress this logical cap to Pise's career.

[2] Partial list:[2] (a response to the anti-Catholic novel Father Clement: A Roman Catholic Story by Grace Kennedy, published in 1823)