Cyriac Pullapilly was born in South India. He was ordained in 1948, and completed his undergraduate studies at the St. Joseph Apostolic seminary, which at its time, was the second-largest seminary in the world. While attending the seminary, he wrote for a missionary publication called Home Field. He also was part of the anti-communist movement in his college and wrote various publications critical of the communist government which controlled the legislature in his state.
In 1975, he founded the Semester Around the World Program, where University of Notre Dame and Saint Mary's College, Indiana, students travelled the world and studied in India.
He has a multi-disciplinary approach to his studies and has published works on a broad range of subjects. His research has been supported by the Fulbright Foundation and the National Endowment for the Humanities, and in 2006 - the year in which he was admitted to the Royal Society of Arts - he held a visiting academic post at the University of Cambridge. He has also established his own publishing company and produced an "inclusive-language" edition of the New Testament.
Based upon his founding of the Semester Around the World program, Pullapilly received the Spes Unica Award from Saint Mary's College for his outstanding service to the College in 2007.
Pullapilly studied at St Thomas College in India and then at the University of Chicago, where he earned his PhD. He and his wife are both Indian immigrants to the United States, raising their children in South Bend, Indiana. Pullapilly is the father of filmmaker Gita Pullapilly.
An only child, Pullapilly's parents were initially reluctant to let him become a priest. Around 1960, he expressed interest in missionary work but said that he did not have the time.