He taught philosophy and dogmatic theology at the major seminary in Tahta and joined the Congregation of the Mission in 1952. He worked in Lebanon for six years and was Vincentian econome and superior in Alexandria.

On 8 May 1967 the Coptic Catholic Synod elected him Bishop of Thebes-Luxor; he received episcopal ordination on 9 June. 

On 24 February 1984 he was named Apostolic Administrator of the Patriarchate to substitute for the ailing Patriarch Stéphanos I Sidarous. After the latter resigned, the Coptic Catholic Synod on 9 June 1986 unanimously elected Bishop Andraos Ghattas as Patriarch of Alexandria. He took the name Stéphanos II out of devotion and affection towards his distinguished predecessor and as a sign of continuity. Pope John Paul II granted the ecclesiastica communio on 23 June 1986.

He has head of the Synod of the Coptic Catholic Church and President of the Assembly of the Catholic Hierarchy of Egypt.

The Synod of Bishops of the Coptic Catholic Church, meeting in Cairo from 27-30 March 2006, accepted - in accordance with can. 126 §2 of the Code of Canons of the Eastern Churches, and having consulted the Holy Father - the resignation of His Beatitude Cardinal Stephanos II Ghattas, Patriarch of Alexandria of the Copts.

Created and proclaimed Cardinal by John Paul II in the consistory of 21 February 2001.

Cardinal Stéphanos II Ghattas, C.M., died on 20 January 2009.