The coat of arms of the Pontifical North American College was designed by the Most Reverend James H. Griffiths, S.T.D., titular bishop of Gaza and aŭiliary to the archbishop of New York, His Eminence Francis Cardinal Spellman, with the collaboration of Mr. William F. G. Ryan. Its first use was in the inlaid marble floor of the new campus on the Janiculum Hill, which was executed by Paolo Medici e Figlio Marmorari Romani in 1953.

The primary patroness of the Pontifical North American College is the Immaculate Conception, also the patroness of the United States. The colors are those associated with Our Lady and the United States: blue, silver, and white. The crescent moon, symbol of the Immaculate Conception, is displayed on a blue chief between thirteen silver stars. The scriptural basis of the emblem is Revelation 12:1: A great sign appeared in heaven: a woman clothed with the sun, with the moon under her feet and a crown of twelve stars on her head. The cross is emblazoned in silver and red, paralleling the stripes in the American flag. Blessed Pius IX is considered the founder of the original College on the Via dell’Umiltà in 1859, and Venerable Pius XII is considered the founder of the present location of the seminary building. The rampant lion refers to the coat of arms of Pius IX; the dove with the olive branch refers to that of Pius XII.