Mathew at the age of 39, received ordination of priesthood from Catholicos Mar Geevarghese II, at Old Seminary.

In July 1963, at the invitation of Russian Orthodox Church, Mar Athanasius and Daniel Mar Philexinos visited Moscow and attended the golden jubilee celebration of the metropolitan consecration of Alexy I Patriarch as the representatives of the Catholicos of the East.

He was installed as Catholicos of the East on the Apostolic throne of St. Thomas on 27 October 1975, succeeding Mar Baselios Augen.

While 'Baselios' has been the traditional formal title of all Catholicoi taken after the great scholar and theologian Mar Baselios of Cappadocia, 'Mar Thoma' was suffixed to imply the lineage of Malankara Metropolitans, in which Mathews I came 18th.

While he was in office, the present system of holding the Holy Episcopal Synod at least twice a year at fixed periods and with proper agendas came into effect.

He consecrated holy Myron, a very rare function, on 1 April 1977 at Old Seminary Chapel, Kottayam and on 25 March 1988 at Devalokam Catholicate Chappel.

He was closely associated with the lawsuits related to factional disputes within the Church when he was a layman and he sought advice on such matters from experts in the field during this time, especially from his elder brother Cherian Vattakunnel.

He was awarded The Order of St. Valdimer by the Patriarch of Russia and made a Fellow of the Leningrad Theological Seminary.

The celebratory meeting held at Kottayam Nehru Stadium on 12 September 1982 had HE Gyani Zail Singh, President of India, as the chief guest.

Dignitaries from several Churches around the world were present at the meeting including Catholicos of All Armenians Vazgen I and Catholicos-Patriarch of All Georgia Ilia II.

During his reign, Mathews I instated the Order of St. Thomas, which is the highest honorary award given by the Indian Orthodox Church.

The first recipient of the award was HE Gyani Zail Singh, the President of India at the Catholicate Platinum Jubilee Celebratory meeting in 1982.

A number of Patriarchs, Catholicoi and Metropolitans from sister Orthodox Churches visited India during his reign.

On 8 February 1986, Pope John Paul II visited Catholicos Mathews I at Mar Elia Cathedral, Kottayam.