Pope Paul VI ordained Burke to the priesthood on June 29th, 1975, for the La Crosse diocese. In 1984 he obtained his PhD in canon law at the Pontifical Gregorian University. On 10th December, 1994, Pope John Paul II named Burke Bishop of La Crosse and subsequently on 2nd December, 2003, Archbishop of St. Louis.
On 27th June 2008, Pope Benedict XVI named Burke Prefect of the Supreme Tribunal of the Apostolic Signatura, of which he was already a member, and President of the Supreme Court of the Vatican City State. In the consistory of 20th November 2010, Pope Benedict XVI created him Cardinal and appointed him Cardinal-Deacon of Sant’Agata dei Goti.
On 8th November, 2014, Pope Francis named Raymond Leo Burke Cardinalis Patronus of the Sovereign Order of Malta, where he succeeded Cardinal Paolo Sardi who has performed this role since June 2009.