Yardumian was born in Philadelphia, Pennsylvania, the youngest of ten children to Armenian immigrant parents, and began studying the piano at a very early age.
Yardumian's earlier compositions frequently reflect the Armenian folk songs and religious melodies he was exposed to as a child.
He was a private in the army during World War II when, in 1945, Eugene Ormandy and the Philadelphia Orchestra premiered Desolate City, which marked Yardumian's debut as a composer.
Throughout the history of their relationship, the Philadelphia Orchestra premiered ten of Yardumian's works, bringing the total of known performances worldwide to nearly 100.
In 1967, Fordham University, in celebration of its 125th anniversary, commissioned Yardumian to write his mass, Come Creator Spirit, which was premiered at Lincoln Center that year with mezzo-soprano Lili Chookasian.