Cardinal Wuerl was born on November 12, 1940 in Pittsburgh.

He was ordained a Priest on December 17, 1966 for the diocese of Pittsburgh, Pennsylvania, USA. He was appointed Auxiliary Bishop of Seattle, Washington, USA and Titular Bishop of Rossmarkaeum on November 30, 1985. His ordination as Bishop took place on January 6, 1986.

On May 26, 1987 he resigned as Auxiliary Bishop of Seattle, Washington, USA, and was appointed Bishop of Pittsburgh, Pennsylvania, USA on February 11, 1988. He was installed there the next day, February 12.

On May 16, 2006 he was appointed Archbishop of Washington, District of Columbia, USA, and was installed there on June 22 of that year.

He was elevated to Cardinal on November 20, 2010, and appointed Cardinal-Priest of San Pietro in Vincoli. He was installed on May 8, 2011.